{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:46:51Z","timestamp":1787028411048,"version":"build-2736575974"},"reference-count":190,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2018,12,24]],"date-time":"2018-12-24T00:00:00Z","timestamp":1545609600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003092","name":"Diabetes Fonds","doi-asserted-by":"publisher","award":["2014.00.1758"],"award-info":[{"award-number":["2014.00.1758"]}],"id":[{"id":"10.13039\/501100003092","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Several diseases are caused by inherited defects in lysosomes, the so-called lysosomal storage disorders (LSDs). In some of these LSDs, tissue macrophages transform into prominent storage cells, as is the case in Gaucher disease. Here, macrophages become the characteristic Gaucher cells filled with lysosomes laden with glucosylceramide, because of their impaired enzymatic degradation. Biomarkers of Gaucher cells were actively searched, particularly after the development of costly therapies based on enzyme supplementation and substrate reduction. Proteins selectively expressed by storage macrophages and secreted into the circulation were identified, among which glycoprotein non-metastatic protein B (GPNMB). This review focusses on the emerging potential of GPNMB as a biomarker of stressed macrophages in LSDs as well as in acquired pathologies accompanied by an excessive lysosomal substrate load in macrophages.<\/jats:p>","DOI":"10.3390\/ijms20010066","type":"journal-article","created":{"date-parts":[[2018,12,24]],"date-time":"2018-12-24T10:37:49Z","timestamp":1545647869000},"page":"66","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":80,"title":["Glycoprotein Non-Metastatic Protein B: An Emerging Biomarker for Lysosomal Dysfunction in Macrophages"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6458-1479","authenticated-orcid":false,"given":"Martijn J.C.","family":"Van der Lienden","sequence":"first","affiliation":[{"name":"Leiden Institute of Chemistry, Leiden University, 2333 CC Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulo","family":"Gaspar","sequence":"additional","affiliation":[{"name":"Leiden Institute of Chemistry, Leiden University, 2333 CC Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf","family":"Boot","sequence":"additional","affiliation":[{"name":"Leiden Institute of Chemistry, Leiden University, 2333 CC Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes M.F.G.","family":"Aerts","sequence":"additional","affiliation":[{"name":"Leiden Institute of Chemistry, Leiden University, 2333 CC Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Van Eijk","sequence":"additional","affiliation":[{"name":"Leiden Institute of Chemistry, Leiden University, 2333 CC Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,12,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1146\/annurev.bi.60.070191.001353","article-title":"Lysosomal Storage Diseases","volume":"60","author":"Neufeld","year":"1991","journal-title":"Annu. Rev. Biochem."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Platt, F.M. (2014). Sphingolipid lysosomal storage disorders. Nature.","DOI":"10.1038\/nature13476"},{"key":"ref_3","first-page":"3635","article-title":"Glucosylceramide Lipidosis-Gaucher Disease","volume":"Volume 8","author":"Scriver","year":"2001","journal-title":"The Metabolic and Molecular Bases of Inherited Diseases"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1172\/JCI105417","article-title":"Demonstration of a deficiency of glucocerebroside-cleaving enzyme in Gaucher\u2019s disease","volume":"45","author":"Brady","year":"1966","journal-title":"J. Clin. Invest."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"8848","DOI":"10.1002\/anie.200902620","article-title":"Glycosphingolipids\u2014Nature, function, and pharmacological modulation","volume":"48","author":"Wennekes","year":"2009","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1586\/epr.09.54","article-title":"Gaucher disease: A model disorder for biomarker discovery","volume":"6","author":"Boot","year":"2009","journal-title":"Expert Rev. Proteomics"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1016\/j.bbalip.2013.11.004","article-title":"Gaucher disease and Fabry disease: New markers and insights in pathophysiology for two distinct glycosphingolipidoses","volume":"1841","author":"Ferraz","year":"2014","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1098\/rstb.2003.1273","article-title":"Biochemistry of glycosphingolipid storage disorders: Implications for therapeutic intervention","volume":"358","author":"Aerts","year":"2003","journal-title":"Philos. Trans. R. Soc. Lond. B. Biol. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1002\/(SICI)1098-1004(1997)10:5<348::AID-HUMU3>3.0.CO;2-B","article-title":"Glucocerebrosidase genotype of Gaucher patients in The Netherlands: Limitations in prognostic value","volume":"10","author":"Boot","year":"1997","journal-title":"Hum. Mutat."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1093\/qjmed\/hch036","article-title":"Twin pairs showing discordance of phenotype in adult Gaucher\u2019s disease","volume":"97","author":"Lachmann","year":"2004","journal-title":"QJM"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.bcmd.2010.10.007","article-title":"A monozygotic twin pair with highly discordant Gaucher phenotypes","volume":"46","author":"Biegstraaten","year":"2011","journal-title":"Blood Cells Mol. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1053\/j.seminhematol.2004.07.009","article-title":"Therapeutic goals in the treatment of Gaucher disease","volume":"41","author":"Pastores","year":"2004","journal-title":"Semin. Hematol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1053\/j.seminhematol.2004.07.010","article-title":"Gaucher disease type 1: Revised recommendations on evaluations and monitoring for adult patients","volume":"41","author":"Weinreb","year":"2004","journal-title":"Semin. Hematol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1007\/s10545-008-0779-z","article-title":"Management of non-neuronopathic Gaucher disease with special reference to pregnancy, splenectomy, bisphosphonate therapy, use of biomarkers and bone disease monitoring","volume":"31","author":"Cox","year":"2008","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1007\/s10545-011-9308-6","article-title":"Biomarkers in the diagnosis of lysosomal storage disorders: Proteins, lipids, and inhibodies","volume":"34","author":"Aerts","year":"2011","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.bbalip.2007.11.004","article-title":"Plasma glucosylceramide and ceramide in type 1 Gaucher disease patients: Correlations with disease severity and response to therapeutic intervention","volume":"1781","author":"Groener","year":"2008","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.cca.2007.12.001","article-title":"Prominent increase in plasma ganglioside GM3 is associated with clinical manifestations of type I Gaucher disease","volume":"389","author":"Langeveld","year":"2008","journal-title":"Clin. Chim. Acta"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e118","DOI":"10.1182\/blood-2011-05-352971","article-title":"Elevated plasma glucosylsphingosine in Gaucher disease: Relation to phenotype, storage cell markers, and therapeutic response","volume":"118","author":"Dekker","year":"2011","journal-title":"Blood"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1002\/ajh.24491","article-title":"Glucosylsphingosine is a key biomarker of Gaucher disease","volume":"91","author":"Murugesan","year":"2016","journal-title":"Am. J. Hematol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1002\/1873-3468.12104","article-title":"Lysosomal glycosphingolipid catabolism by acid ceramidase: Formation of glycosphingoid bases during deficiency of glycosidases","volume":"590","author":"Ferraz","year":"2016","journal-title":"FEBS Lett."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1194\/jlr.M043802","article-title":"Action myoclonus-renal failure syndrome: Diagnostic applications of activity-based probes and lipid analysis","volume":"55","author":"Gaspar","year":"2014","journal-title":"J. Lipid Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1016\/j.cell.2007.10.018","article-title":"LIMP-2 Is a Receptor for Lysosomal Mannose-6-Phosphate-Independent Targeting of \u03b2-Glucocerebrosidase","volume":"131","author":"Reczek","year":"2007","journal-title":"Cell"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2238","DOI":"10.1093\/hmg\/ddn124","article-title":"A nonsense mutation in the LIMP-2 gene associated with progressive myoclonic epilepsy and nephrotic syndrome","volume":"17","author":"Balreira","year":"2008","journal-title":"Hum. Mol. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.bcmd.2015.01.006","article-title":"Mass spectrometric quantification of glucosylsphingosine in plasma and urine of type 1 Gaucher patients using an isotope standard","volume":"54","author":"Mirzaian","year":"2015","journal-title":"Blood Cells Mol. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.ymgme.2017.08.005","article-title":"Reductions in glucosylsphingosine (lyso-Gb1) in treatment-na\u00efve and previously treated patients receiving velaglucerase alfa for type 1 Gaucher disease: Data from phase 3 clinical trials","volume":"122","author":"Elstein","year":"2017","journal-title":"Mol. Genet. Metab."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.ymgme.2015.12.006","article-title":"Lyso-glycosphingolipid abnormalities in different murine models of lysosomal storage disorders","volume":"117","author":"Ferraz","year":"2016","journal-title":"Mol. Genet. Metab."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1023\/A:1022436928925","article-title":"Twenty Five Years of the \u201cPsychosine Hypothesis\u201d: A Personal Perspective of its History and Present Status","volume":"23","author":"Suzuki","year":"1998","journal-title":"Neurochem. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2812","DOI":"10.1073\/pnas.0712309105","article-title":"Elevated globotriaosylsphingosine is a hallmark of Fabry disease","volume":"105","author":"Aerts","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.ab.2017.02.019","article-title":"Quantitation of plasmatic lysosphingomyelin and lysosphingomyelin-509 for differential screening of Niemann-Pick A\/B and C diseases","volume":"525","author":"Kuchar","year":"2017","journal-title":"Anal. Biochem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.cca.2017.01.014","article-title":"Simultaneous quantitation of sphingoid bases by UPLC-ESI-MS\/MS with identical 13C-encoded internal standards","volume":"466","author":"Mirzaian","year":"2017","journal-title":"Clin. Chim. Acta"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Pettazzoni, M., Froissart, R., Pagan, C., Vanier, M.T., Ruet, S., Latour, P., Guffon, N., Fouilhoux, A., Germain, D.P., and Levade, T. (2017). LC-MS\/MS multiplex analysis of lysosphingolipids in plasma and amniotic fluid: A novel tool for the screening of sphingolipidoses and Niemann-Pick type C disease. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0181700"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1515\/cclm-2016-0340","article-title":"Diagnosis of sphingolipidoses: A new simultaneous measurement of lysosphingolipids by LC-MS\/MS","volume":"55","author":"Polo","year":"2017","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"19473","DOI":"10.1073\/pnas.1003308107","article-title":"Glucocerebrosidase gene-deficient mouse recapitulates Gaucher disease displaying cellular and molecular dysregulation beyond the macrophage","volume":"107","author":"Mistry","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1056\/NEJMoa1508808","article-title":"Clonal Immunoglobulin against Lysolipids in the Origin of Myeloma","volume":"374","author":"Nair","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1002\/path.4227","article-title":"B cell lymphoma and myeloma in murine Gaucher\u2019s disease","volume":"231","author":"Pavlova","year":"2013","journal-title":"J. Pathol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Lukas, J., Cozma, C., Yang, F., Kramp, G., Meyer, A., Ne\u00dflauer, A.-M., Eichler, S., B\u00f6ttcher, T., Witt, M., and Br\u00e4uer, A.U. (2017). Glucosylsphingosine Causes Hematological and Visceral Changes in Mice-Evidence for a Pathophysiological Role in Gaucher Disease. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18102192"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"9617","DOI":"10.1523\/JNEUROSCI.1525-17.2017","article-title":"Glucosylsphingosine promotes \u03b1-synuclein pathology in mutant GBA-associated Parkinson\u2019s Disease","volume":"37","author":"Taguchi","year":"2017","journal-title":"J. Neurosci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1056\/NEJMoa0901281","article-title":"Multicenter Analysis of Glucocerebrosidase Mutations in Parkinson\u2019s Disease","volume":"361","author":"Sidransky","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.neulet.2015.01.084","article-title":"The Fabry disease-associated lipid Lyso-Gb3 enhances voltage-gated calcium currents in sensory neurons and causes pain","volume":"594","author":"Choi","year":"2015","journal-title":"Neurosci. Lett."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"5720","DOI":"10.1093\/hmg\/ddv291","article-title":"Lyso-Gb3 activates Notch1 in human podocytes","volume":"24","author":"Carpio","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Aerts, J.M., Ferraz, M.J., Mirzaian, M., Gaspar, P., Oussoren, S.V., Wisse, P., Kuo, C.-L., Lelieveld, L.T., Kytidou, K., and Hazeu, M.D. (2017). Lysosomal Storage Diseases. For Better or Worse: Adapting to Defective Lysosomal Glycosphingolipid Breakdown. eLS, John Wiley & Sons, Ltd.","DOI":"10.1002\/9780470015902.a0027592"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1194\/jlr.M064923","article-title":"Glucosylated cholesterol in mammalian cells and tissues: Formation and degradation by multiple cellular \u03b2-glucosidases","volume":"57","author":"Marques","year":"2016","journal-title":"J. Lipid Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1016\/j.bbrc.2013.10.145","article-title":"Cholesterol glucosylation is catalyzed by transglucosylation reaction of \u03b2-glucosidase 1","volume":"441","author":"Akiyama","year":"2013","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.ymgme.2009.06.008","article-title":"Recommendations on the diagnosis and management of Niemann-Pick disease type C","volume":"98","author":"Wraith","year":"2009","journal-title":"Mol. Genet. Metab."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"56ra81","DOI":"10.1126\/scitranslmed.3001417","article-title":"Cholesterol oxidation products are sensitive and specific blood-based biomarkers for Niemann-Pick C1 disease","volume":"2","author":"Porter","year":"2010","journal-title":"Sci. Transl. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1023\/A:1005474803278","article-title":"Cholesterol and oxygenated cholesterol concentrations are markedly elevated in peripheral tissue but not in brain from mice with the Niemann\u2013Pick type C phenotype","volume":"21","author":"Tint","year":"1998","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1194\/jlr.D015735","article-title":"A sensitive and specific LC-MS\/MS method for rapid diagnosis of Niemann-Pick C1 disease from human plasma","volume":"52","author":"Jiang","year":"2011","journal-title":"J. Lipid Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.ijdevneu.2017.11.007","article-title":"Molecular and biochemical biomarkers for diagnosis and therapy monitorization of Niemann-Pick type C patients","volume":"66","author":"Hammerschmidt","year":"2018","journal-title":"Int. J. Dev. Neurosci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1515\/cclm-2015-0669","article-title":"High level of oxysterols in neonatal cholestasis: A pitfall in analysis of biochemical markers for Niemann-Pick type C disease","volume":"54","author":"Polo","year":"2016","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.patbio.2004.11.002","article-title":"High circulating levels of 7\u03b2- and 7\u03b1-hydroxycholesterol and presence of apoptotic and oxidative markers in arterial lesions of normocholesterolemic atherosclerotic patients undergoing endarterectomy","volume":"54","author":"Prunet","year":"2006","journal-title":"Pathol. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1002\/dmrr.645","article-title":"Cholesterol oxides as biomarkers of oxidative stress in type 1 and type 2 diabetes mellitus","volume":"23","author":"Ferderbar","year":"2007","journal-title":"Diabetes Metab. Res. Rev."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"4282","DOI":"10.1210\/jc.2008-0586","article-title":"Oxysterol as a Marker of Atherogenic Dyslipidemia in Adolescence","volume":"93","author":"Alkazemi","year":"2008","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Marques, A.R.A., Aten, J., Ottenhoff, R., van Roomen, C.P.A.A., Herrera Moro, D., Claessen, N., Vinueza Veloz, M.F., Zhou, K., Lin, Z., and Mirzaian, M. (2015). Reducing GBA2 Activity Ameliorates Neuropathology in Niemann-Pick Type C Mice. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0135889"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1016\/S0140-6736(00)02161-9","article-title":"Novel oral treatment of Gaucher\u2019s disease with N-butyldeoxynojirimycin (OGT 918) to decrease substrate biosynthesis","volume":"355","author":"Cox","year":"2000","journal-title":"Lancet"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1023\/A:1010335505357","article-title":"Inhibition of substrate synthesis as a strategy for glycolipid lysosomal storage disease therapy","volume":"24","author":"Platt","year":"2001","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1007\/s10545-006-0272-5","article-title":"Substrate reduction therapy of glycosphingolipid storage disorders","volume":"29","author":"Aerts","year":"2006","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1016\/S1474-4422(07)70194-1","article-title":"Miglustat for treatment of Niemann-Pick C disease: A randomised controlled study","volume":"6","author":"Patterson","year":"2007","journal-title":"Lancet Neurol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1111\/j.1651-2227.2005.tb02110.x","article-title":"Identification and use of biomarkers in Gaucher disease and other lysosomal storage diseases","volume":"94","author":"Aerts","year":"2007","journal-title":"Acta Paediatr."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1098\/rstb.2003.1269","article-title":"Enzyme replacement therapy: Conception, chaos and culmination","volume":"358","author":"Brady","year":"2003","journal-title":"Philos. Trans. R. Soc. Lond. B. Biol. Sci."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Barton, N.W., Furbish, F.S., Murray, G.J., Garfield, M., and Brady, R.O. (1990). Therapeutic response to intravenous infusions of glucocerebrosidase in a patient with Gaucher disease. Proc. Natl. Acad. Sci., 87.","DOI":"10.1073\/pnas.87.5.1913"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1001\/jama.1996.03530310054033","article-title":"Gaucher Disease","volume":"275","author":"McCabe","year":"1996","journal-title":"JAMA"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1056\/NEJM199305273282112","article-title":"Treatment of Gaucher\u2019s Disease","volume":"328","author":"Hollak","year":"1993","journal-title":"N. Engl. J. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1016\/S0950-3536(97)80034-0","article-title":"4 Plasma and metabolic abnormalities in Gaucher\u2019s disease","volume":"10","author":"Aerts","year":"1997","journal-title":"Baillieres. Clin. Haematol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1002\/cbf.1133","article-title":"Tartrate-resistant acid phosphatase: A potential target for therapeutic gold","volume":"22","author":"Hayman","year":"2004","journal-title":"Cell Biochem. Funct."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1172\/JCI117084","article-title":"Marked elevation of plasma chitotriosidase activity. A novel hallmark of Gaucher disease","volume":"93","author":"Hollak","year":"1994","journal-title":"J. Clin. Invest."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2198","DOI":"10.1074\/jbc.270.5.2198","article-title":"Purification and characterization of human chitotriosidase, a novel member of the chitinase family of proteins","volume":"270","author":"Renkema","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"26252","DOI":"10.1074\/jbc.270.44.26252","article-title":"Cloning of a cDNA encoding chitotriosidase, a human chitinase produced by macrophages","volume":"270","author":"Boot","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1111\/j.1432-1033.1997.00279.x","article-title":"Synthesis, Sorting, and Processing into Distinct Isoforms of Human Macrophage Chitotriosidase","volume":"244","author":"Renkema","year":"1997","journal-title":"Eur. J. Biochem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"25680","DOI":"10.1074\/jbc.273.40.25680","article-title":"The human chitotriosidase gene. Nature of inherited enzyme deficiency","volume":"273","author":"Boot","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"25537","DOI":"10.1074\/jbc.M201636200","article-title":"Structure of human chitotriosidase. Implications for specific inhibitor design and function of mammalian chitinase-like lectins","volume":"277","author":"Fusetti","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1309\/BG5VA8JRDQH1M7HN","article-title":"Gaucher Cells Demonstrate a Distinct Macrophage Phenotype and Resemble Alternatively Activated Macrophages","volume":"122","author":"Boven","year":"2004","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1093\/intimm\/dxh328","article-title":"Characterization of human phagocyte-derived chitotriosidase, a component of innate immunity","volume":"17","author":"Renkema","year":"2005","journal-title":"Int. Immunol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S0074-7696(06)52001-7","article-title":"The Biology of the Gaucher Cell: The Cradle of Human Chitinases","volume":"252","author":"Bussink","year":"2006","journal-title":"Int. Rev. Cytol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1534\/genetics.107.075846","article-title":"Evolution of mammalian chitinase(-like) members of family 18 glycosyl hydrolases","volume":"177","author":"Bussink","year":"2007","journal-title":"Genetics"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"40911","DOI":"10.1074\/jbc.M301804200","article-title":"Transglycosidase activity of chitotriosidase: Improved enzymatic assay for the human macrophage chitinase","volume":"278","author":"Aguilera","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.cca.2007.02.042","article-title":"Monitoring of Gaucher patients with a novel chitotriosidase assay","volume":"381","author":"Schoonhoven","year":"2007","journal-title":"Clin. Chim. Acta"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1007\/s10545-014-9711-x","article-title":"Value of plasma chitotriosidase to assess non-neuronopathic Gaucher disease severity and progression in the era of enzyme replacement therapy","volume":"37","author":"Hendriks","year":"2014","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1161\/01.ATV.19.3.687","article-title":"Strong Induction of Members of the Chitinase Family of Proteins in Atherosclerosis","volume":"19","author":"Boot","year":"1999","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/j.clim.2009.02.003","article-title":"Increased chitotriosidase activity in serum of leprosy patients: Association with bacillary leprosy","volume":"131","author":"Iyer","year":"2009","journal-title":"Clin. Immunol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.cca.2009.09.034","article-title":"Plasma chitotriosidase and CCL18 as surrogate markers for granulomatous macrophages in sarcoidosis","volume":"411","author":"Boot","year":"2010","journal-title":"Clin. Chim. Acta"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1007\/BF02436762","article-title":"Elevated plasma chitotriosidase activity in various lysosomal storage disorders","volume":"18","author":"Guo","year":"1995","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.ymgme.2006.04.013","article-title":"Plasma chitotriosidase in male Fabry patients: A marker for monitoring lipid-laden macrophages and their correction by enzyme replacement therapy","volume":"89","author":"Vedder","year":"2006","journal-title":"Mol. Genet. Metab."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1007\/s10545-006-0363-3","article-title":"Critical assessment of chitotriosidase analysis in the rational laboratory diagnosis of children with Gaucher disease and Niemann\u2013Pick disease type A\/B and C","volume":"29","author":"Ries","year":"2006","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1969","DOI":"10.1182\/blood.V96.5.1969","article-title":"Pathologic gene expression in Gaucher disease: Up-regulation of cysteine proteinases including osteoclastic cathepsin K","volume":"96","author":"Moran","year":"2000","journal-title":"Blood"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1182\/blood-2003-05-1612","article-title":"Marked elevation of the chemokine CCL18\/PARC in Gaucher disease: A novel surrogate marker for assessing therapeutic intervention","volume":"103","author":"Boot","year":"2004","journal-title":"Blood"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.bcmd.2005.05.005","article-title":"Clinical evaluation of chemokine and enzymatic biomarkers of Gaucher disease","volume":"35","author":"Deegan","year":"2005","journal-title":"Blood Cells Mol. Dis."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.bcmd.2009.09.005","article-title":"CCL18 as an alternative marker in Gaucher and Niemann-Pick disease with chitotriosidase deficiency","volume":"44","author":"Chang","year":"2010","journal-title":"Blood Cells Mol. Dis."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/j.ymgme.2009.11.007","article-title":"Clinical experience with miglustat therapy in pediatric patients with Niemann-Pick disease type C: A case series","volume":"99","author":"Pineda","year":"2010","journal-title":"Mol. Genet. Metab."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/s12967-017-1146-3","article-title":"Assessment of plasma chitotriosidase activity, CCL18\/PARC concentration and NP-C suspicion index in the diagnosis of Niemann-Pick disease type C: A prospective observational study","volume":"15","author":"Cebolla","year":"2017","journal-title":"J. Transl. Med."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1038\/nrd3311","article-title":"Velaglucerase alfa","volume":"9","author":"Aerts","year":"2010","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"5767","DOI":"10.1182\/blood-2011-07-366955","article-title":"Pivotal trial with plant cell-expressed recombinant glucocerebrosidase, taliglucerase alfa, a novel enzyme replacement therapy for Gaucher disease","volume":"118","author":"Zimran","year":"2011","journal-title":"Blood"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1023\/B:BOLI.0000045756.54006.17","article-title":"Sustained therapeutic effects of oral miglustat (Zavesca, N-butyldeoxynojirimycin, OGT 918) in type I Gaucher disease","volume":"27","author":"Elstein","year":"2004","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2355","DOI":"10.1016\/S0140-6736(14)61841-9","article-title":"Eliglustat compared with imiglucerase in patients with Gaucher\u2019s disease type 1 stabilised on enzyme replacement therapy: A phase 3, randomised, open-label, non-inferiority trial","volume":"385","author":"Cox","year":"2015","journal-title":"Lancet"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1001\/jama.2015.459","article-title":"Effect of Oral Eliglustat on Splenomegaly in Patients With Gaucher Disease Type 1","volume":"313","author":"Mistry","year":"2015","journal-title":"JAMA"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s13023-016-0413-3","article-title":"Biochemical response to substrate reduction therapy versus enzyme replacement therapy in Gaucher disease type 1 patients","volume":"11","author":"Smid","year":"2016","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1182\/blood.V89.1.315","article-title":"Enhancement of macrophage colony-stimulating factor-induced growth and differentiation of human monocytes by interleukin-10","volume":"89","author":"Hashimoto","year":"1997","journal-title":"Blood"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1002\/2211-5463.12078","article-title":"Elevation of glycoprotein nonmetastatic melanoma protein B in type 1 Gaucher disease patients and mouse models","volume":"6","author":"Kramer","year":"2016","journal-title":"FEBS Open Bio."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1038\/mt.2015.16","article-title":"Lentiviral gene therapy using cellular promoters cures type 1 Gaucher disease in mice","volume":"23","author":"Dahl","year":"2015","journal-title":"Mol. Ther."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1002\/path.4452","article-title":"Inhibition of UDP-glucosylceramide synthase in mice prevents Gaucher disease-associated B-cell malignancy","volume":"235","author":"Pavlova","year":"2015","journal-title":"J. Pathol."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Xu, Y.-H., Jia, L., Quinn, B., Zamzow, M., Stringer, K., Aronow, B., Sun, Y., Zhang, W., Setchell, K.D., and Grabowski, G.A. (2011). Global gene expression profile progression in Gaucher disease mouse models. BMC Genomics, 12.","DOI":"10.1186\/1471-2164-12-20"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Zigdon, H., Savidor, A., Levin, Y., Meshcheriakova, A., Schiffmann, R., and Futerman, A.H. (2015). Identification of a biomarker in cerebrospinal fluid for neuronopathic forms of Gaucher disease. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0120194"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.bcmd.2016.12.002","article-title":"Validating glycoprotein non-metastatic melanoma B (gpNMB, osteoactivin), a new biomarker of Gaucher disease","volume":"68","author":"Murugesan","year":"2018","journal-title":"Blood Cells Mol. Dis."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Marques, A.R.A., Gabriel, T.L., Aten, J., van Roomen, C.P.A.A., Ottenhoff, R., Claessen, N., Alfonso, P., Ir\u00fan, P., Giraldo, P., and Aerts, J.M.F.G. (2016). Gpnmb Is a Potential Marker for the Visceral Pathology in Niemann-Pick Type C Disease. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0147208"},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Alam, M.S., Getz, M., Safeukui, I., Yi, S., Tamez, P., Shin, J., Vel\u00e1zquez, P., and Haldar, K. (2012). Genomic Expression Analyses Reveal Lysosomal, Innate Immunity Proteins, as Disease Correlates in Murine Models of a Lysosomal Storage Disorder. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0048273"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"3632","DOI":"10.1093\/hmg\/dds193","article-title":"Microarray expression analysis and identification of serum biomarkers for Niemann\u2013Pick disease, type C1","volume":"21","author":"Cluzeau","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"ref_106","unstructured":"(2018, November 24). UniProtKB-Q14956. Available online: https:\/\/www.uniprot.org\/uniprot\/Q14956."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"16899","DOI":"10.1073\/pnas.242603899","article-title":"Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences","volume":"99","author":"Strausberg","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_108","unstructured":"(2018, November 24). UniProtKB-Q99P91. Available online: https:\/\/www.uniprot.org\/uniprot\/Q99P91."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"8125","DOI":"10.1074\/jbc.M008539200","article-title":"Molecular cloning of a dendritic cell-associated transmembrane protein, DC-HIL, that promotes RGD-dependent adhesion of endothelial cells through recognition of heparan sulfate proteoglycans","volume":"276","author":"Shikano","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1616","DOI":"10.1096\/fj.09-151019","article-title":"Glycoprotein nonmetastatic melanoma protein b, a melanocytic cell marker, is a melanosome-specific and proteolytically released protein","volume":"24","author":"Hoashi","year":"2010","journal-title":"FASEB J."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"5743","DOI":"10.1016\/j.febslet.2007.11.036","article-title":"Osteoactivin fragments produced by ectodomain shedding induce MMP-3 expression via ERK pathway in mouse NIH-3T3 fibroblasts","volume":"581","author":"Furochi","year":"2007","journal-title":"FEBS Lett."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Rose, A.A.N., Annis, M.G., Dong, Z., Pepin, F., Hallett, M., Park, M., and Siegel, P.M. (2010). ADAM10 releases a soluble form of the GPNMB\/Osteoactivin extracellular domain with angiogenic properties. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0012093"},{"key":"ref_113","first-page":"4767","article-title":"The melanoma-associated transmembrane glycoprotein Gpnmb controls trafficking of cellular debris for degradation and is essential for tissue repair","volume":"24","author":"Li","year":"2010","journal-title":"FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1111\/pcmr.12084","article-title":"The PKD domain distinguishes the trafficking and amyloidogenic properties of the pigment cell protein PMEL and its homologue GPNMB","volume":"26","author":"Theos","year":"2013","journal-title":"Pigment Cell Melanoma Res."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/ijc.2910600111","article-title":"nmb, a novel gene, is expressed in low-metastatic human melanoma cell lines and xenografts","volume":"60","author":"Weterman","year":"1995","journal-title":"Int. J. Cancer"},{"key":"ref_116","unstructured":"(2018, December 03). Tissue expression of GPNMB-Summary-The Human Protein Atlas. Available online: https:\/\/www.proteinatlas.org\/ENSG00000136235-GPNMB\/tissue."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"6557","DOI":"10.4049\/jimmunol.178.10.6557","article-title":"Gpnmb is induced in macrophages by IFN-gamma and lipopolysaccharide and acts as a feedback regulator of proinflammatory responses","volume":"178","author":"Ripoll","year":"2007","journal-title":"J. Immunol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1016\/j.febslet.2008.03.030","article-title":"Osteoactivin is a novel osteoclastic protein and plays a key role in osteoclast differentiation and activity","volume":"582","author":"Sheng","year":"2008","journal-title":"FEBS Lett."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.gene.2008.01.014","article-title":"Microphthalmia transcription factor regulates the expression of the novel osteoclast factor GPNMB","volume":"413","author":"Ripoll","year":"2008","journal-title":"Gene"},{"key":"ref_120","first-page":"839","article-title":"Glycoprotein non-metastatic b (GPNMB): A metastatic mediator and emerging therapeutic target in cancer","volume":"6","author":"Maric","year":"2013","journal-title":"Onco. Targets. Ther."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"2831","DOI":"10.1242\/jcs.114.15.2831","article-title":"The AP-3-dependent targeting of the melanosomal glycoprotein QNR-71 requires a di-leucine-based sorting signal","volume":"114","author":"Planque","year":"2001","journal-title":"J. Cell Sci."},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Zhang, P., Liu, W., Zhu, C., Yuan, X., Li, D., Gu, W., Ma, H., Xie, X., and Gao, T. (2012). Silencing of GPNMB by siRNA Inhibits the Formation of Melanosomes in Melanocytes in a MITF-Independent Fashion. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0042955"},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Anderson, M.G., Libby, R.T., Mao, M., Cosma, I.M., Wilson, L.A., Smith, R.S., and John, S.W. (2006). Genetic context determines susceptibility to intraocular pressure elevation in a mouse pigmentary glaucoma. BMC Biol., 4.","DOI":"10.1186\/1741-7007-4-20"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1038\/ng794","article-title":"Mutations in genes encoding melanosomal proteins cause pigmentary glaucoma in DBA\/2J mice","volume":"30","author":"Anderson","year":"2001","journal-title":"Nat. Genet."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.ajhg.2017.12.012","article-title":"Loss of GPNMB Causes Autosomal-Recessive Amyloidosis Cutis Dyschromica in Humans","volume":"102","author":"Yang","year":"2018","journal-title":"Am. J. Hum. Genet."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/S0167-0115(02)00288-4","article-title":"Hematopoietic growth factor inducible neurokinin-1 type: A transmembrane protein that is similar to neurokinin 1 interacts with substance P","volume":"111","author":"Bandari","year":"2003","journal-title":"Regul. Pept."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1002\/jcb.1259","article-title":"Cloning and Characterization of Osteoactivin, A Novel cDNA Expressed in Osteoblasts","volume":"84","author":"Safadi","year":"2002","journal-title":"J. Cell. Biochem."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"3338","DOI":"10.1002\/j.1460-2075.1996.tb00699.x","article-title":"Characterization of a new melanocyte-specific gene (QNR-71) expressed in v-myc-transformed quail neuroretina","volume":"15","author":"Turque","year":"1996","journal-title":"EMBO J."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"6930","DOI":"10.1128\/MCB.18.12.6930","article-title":"Targeting the microphthalmia basic helix-loop-helix-leucine zipper transcription factor to a subset of E-box elements in vitro and in vivo","volume":"18","author":"Aksan","year":"1998","journal-title":"Mol. Cell. Biol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/S0002-9440(10)63657-7","article-title":"MLANA\/MART1 and SILV\/PMEL17\/GP100 are transcriptionally regulated by MITF in melanocytes and melanoma","volume":"163","author":"Du","year":"2003","journal-title":"Am. J. Pathol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s12964-015-0099-5","article-title":"The transcription factor MITF is a critical regulator of GPNMB expression in dendritic cells","volume":"13","author":"Gutknecht","year":"2015","journal-title":"Cell Commun. Signal."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"3310","DOI":"10.2337\/db13-1720","article-title":"Lysosomal stress in obese adipose tissue macrophages contributes to MITF-dependent Gpnmb induction","volume":"63","author":"Gabriel","year":"2014","journal-title":"Diabetes"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"2483","DOI":"10.1007\/s00018-014-1565-8","article-title":"Novel roles for the MiTF\/TFE family of transcription factors in organelle biogenesis, nutrient sensing, and energy homeostasis","volume":"71","author":"Martina","year":"2014","journal-title":"Cell. Mol. life Sci. C."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/15548627.2015.1100356","article-title":"Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)","volume":"12","author":"Klionsky","year":"2016","journal-title":"Autophagy"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1126\/science.1204592","article-title":"TFEB Links Autophagy to Lysosomal Biogenesis","volume":"332","author":"Settembre","year":"2011","journal-title":"Science"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/S0168-9525(00)89143-X","article-title":"Insight into the microphthalmia gene","volume":"11","author":"Moore","year":"1995","journal-title":"Trends Genet."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"2770","DOI":"10.1101\/gad.8.22.2770","article-title":"microphthalmia, a critical factor in melanocyte development, defines a discrete transcription factor family","volume":"8","author":"Hemesath","year":"1994","journal-title":"Genes Dev."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"2647","DOI":"10.1101\/gad.198192.112","article-title":"Restricted leucine zipper dimerization and specificity of DNA recognition of the melanocyte master regulator MITF","volume":"26","author":"Pogenberg","year":"2012","journal-title":"Genes Dev."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1083\/jcb.201209135","article-title":"Rag GTPases mediate amino acid-dependent recruitment of TFEB and MITF to lysosomes","volume":"200","author":"Martina","year":"2013","journal-title":"J. Cell Biol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"14338","DOI":"10.1038\/ncomms14338","article-title":"mTORC1-independent TFEB activation via Akt inhibition promotes cellular clearance in neurodegenerative storage diseases","volume":"8","author":"Palmieri","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1093\/hmg\/9.1.125","article-title":"Ser298 of MITF, a mutation site in Waardenburg syndrome type 2, is a phosphorylation site with functional significance","volume":"9","author":"Takeda","year":"2000","journal-title":"Hum. Mol. Genet."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"4320","DOI":"10.1182\/blood-2006-11-053769","article-title":"DC-HIL is a negative regulator of T lymphocyte activation","volume":"109","author":"Chung","year":"2007","journal-title":"Blood"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"5778","DOI":"10.4049\/jimmunol.179.9.5778","article-title":"Syndecan-4 mediates the coinhibitory function of DC-HIL on T cell activation","volume":"179","author":"Chung","year":"2007","journal-title":"J. Immunol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1002\/eji.200838990","article-title":"The DC-HIL\/syndecan-4 pathway inhibits human allogeneic T-cell responses","volume":"39","author":"Chung","year":"2009","journal-title":"Eur. J. Immunol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"2576","DOI":"10.4049\/jimmunol.1301857","article-title":"The DC-HIL\/syndecan-4 pathway regulates autoimmune responses through myeloid-derived suppressor cells","volume":"192","author":"Chung","year":"2014","journal-title":"J. Immunol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1006\/excr.1998.4108","article-title":"Structural Requirements for \u03b19\u03b21-Mediated Adhesion and Migration to Thrombin-Cleaved Osteopontin","volume":"242","author":"Smith","year":"1998","journal-title":"Exp. Cell Res."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1083\/jcb.149.2.521","article-title":"Defining fibronectin\u2019s cell adhesion synergy site by site-directed mutagenesis","volume":"149","author":"Redick","year":"2000","journal-title":"J. Cell Biol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1111\/j.1600-0625.2008.00830.x","article-title":"Gpnmb is a melanosome-associated glycoprotein that contributes to melanocyte\/keratinocyte adhesion in a RGD-dependent fashion","volume":"18","author":"Tomihari","year":"2009","journal-title":"Exp. Dermatol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1002\/jcb.25394","article-title":"Macrophage-Associated Osteoactivin\/GPNMB Mediates Mesenchymal Stem Cell Survival, Proliferation, and Migration Via a CD44-Dependent Mechanism","volume":"117","author":"Yu","year":"2016","journal-title":"J. Cell. Biochem."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.jid.2017.08.034","article-title":"Glycoprotein Nonmelanoma Clone B Regulates the Crosstalk between Macrophages and Mesenchymal Stem Cells toward Wound Repair","volume":"138","author":"Yu","year":"2018","journal-title":"J. Invest. Dermatol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"2729","DOI":"10.1002\/jcb.24621","article-title":"GPNMB enhances bone regeneration by promoting angiogenesis and osteogenesis: Potential role for tissue engineering bone","volume":"114","author":"Hu","year":"2013","journal-title":"J. Cell. Biochem."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"2334","DOI":"10.1016\/j.yexcr.2008.02.006","article-title":"Osteoactivin, an anabolic factor that regulates osteoblast differentiation and function","volume":"314","author":"Abdelmagid","year":"2008","journal-title":"Exp. Cell Res."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"16920","DOI":"10.1038\/srep16920","article-title":"Beneficial impact of Gpnmb and its significance as a biomarker in nonalcoholic steatohepatitis","volume":"5","author":"Katayama","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1016\/S0168-8278(03)00361-1","article-title":"Osteoactivin expressed during cirrhosis development in rats fed a choline-deficient, l-amino acid-defined diet, accelerates motility of hepatoma cells","volume":"39","author":"Onaga","year":"2003","journal-title":"J. Hepatol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/j.jhep.2004.12.021","article-title":"Expression of osteoactivin in rat and human liver and isolated rat liver cells","volume":"42","author":"Ramadori","year":"2005","journal-title":"J. Hepatol."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"2771","DOI":"10.1113\/jphysiol.2014.272864","article-title":"Astrocyte calcium signaling orchestrates neuronal synchronization in organotypic hippocampal slices","volume":"592","author":"Sasaki","year":"2014","journal-title":"J. Physiol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1038\/ki.2011.28","article-title":"Hematopoietic growth factor inducible neurokinin-1 (Gpnmb\/Osteoactivin) is a biomarker of progressive renal injury across species","volume":"79","author":"Wang","year":"2011","journal-title":"Kidney Int."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"E3186","DOI":"10.1073\/pnas.1119964109","article-title":"Differential Ly-6C expression identifies the recruited macrophage phenotype, which orchestrates the regression of murine liver fibrosis","volume":"109","author":"Ramachandran","year":"2012","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1016\/j.bbrc.2007.03.035","article-title":"Transgenic expression of osteoactivin in the liver attenuates hepatic fibrosis in rats","volume":"356","author":"Abe","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_160","doi-asserted-by":"crossref","unstructured":"Kumagai, K., Tabu, K., Sasaki, F., Takami, Y., Morinaga, Y., Mawatari, S., Hashimoto, S., Tanoue, S., Kanmura, S., and Tamai, T. (2015). Glycoprotein Nonmetastatic Melanoma B (Gpnmb)-Positive Macrophages Contribute to the Balance between Fibrosis and Fibrolysis during the Repair of Acute Liver Injury in Mice. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0143413"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"56","DOI":"10.2215\/CJN.03390509","article-title":"Upregulation of monocyte\/macrophage HGFIN (Gpnmb\/Osteoactivin) expression in end-stage renal disease","volume":"5","author":"Pahl","year":"2010","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"7503","DOI":"10.3892\/mmr.2015.4408","article-title":"Expression of glycoprotein nonmetastatic melanoma protein B in macrophages infiltrating injured mucosa is associated with the severity of experimental colitis in mice","volume":"12","author":"Sasaki","year":"2015","journal-title":"Mol. Med. Rep."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.ymgme.2018.02.012","article-title":"Increased GPNMB, phospho-ERK1\/2, and MMP-9 in cystic fibrosis in association with reduced arylsulfatase B","volume":"124","author":"Bhattacharyya","year":"2018","journal-title":"Mol. Genet. Metab."},{"key":"ref_164","first-page":"590","article-title":"An ultrastructural and experimental study on the development of tubular structures in the lysosomes of Gaucher cells","volume":"58","author":"Naito","year":"1988","journal-title":"Lab. Invest."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1016\/j.bbadis.2007.04.002","article-title":"Increased plasma macrophage inflammatory protein (MIP)-1\u03b1 and MIP-1\u03b2 levels in type 1 Gaucher disease","volume":"1772","author":"Voerman","year":"2007","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_166","doi-asserted-by":"crossref","unstructured":"Lombardo, E., van Roomen, C.P.A.A., van Puijvelde, G.H., Ottenhoff, R., van Eijk, M., Aten, J., Kuiper, J., Overkleeft, H.S., Groen, A.K., and Verhoeven, A.J. (2012). Correction of Liver Steatosis by a Hydrophobic Iminosugar Modulating Glycosphingolipids Metabolism. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0038520"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"1810","DOI":"10.3389\/fimmu.2017.01810","article-title":"Gene Expression Profiling of Multiple Sclerosis Pathology Identifies Early Patterns of Demyelination Surrounding Chronic Active Lesions","volume":"8","author":"Hendrickx","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.atherosclerosis.2015.07.001","article-title":"Modelling atherosclerosis by proteomics: Molecular changes in the ascending aortas of cholesterol-fed rabbits","volume":"242","author":"Xu","year":"2015","journal-title":"Atherosclerosis"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1016\/j.cmet.2013.11.001","article-title":"Obesity activates a program of lysosomal-dependent lipid metabolism in adipose tissue macrophages independently of classic activation","volume":"18","author":"Xu","year":"2013","journal-title":"Cell Metab."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/15548627.2017.1419118","article-title":"HEPES activates a MiT\/TFE-dependent lysosomal-autophagic gene network in cultured cells: A call for caution","volume":"14","author":"Tol","year":"2018","journal-title":"Autophagy"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1038\/emboj.2012.32","article-title":"A lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB","volume":"31","author":"Settembre","year":"2012","journal-title":"EMBO J."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.1002\/glia.23034","article-title":"The novel monoclonal antibody 9F5 reveals expression of a fragment of GPNMB\/osteoactivin processed by furin-like protease(s) in a subpopulation of microglia in neonatal rat brain","volume":"64","author":"Kawahara","year":"2016","journal-title":"Glia"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1002\/brb3.39","article-title":"Expression and immunolocalization of Gpnmb, a glioma-associated glycoprotein, in normal and inflamed central nervous systems of adult rats","volume":"2","author":"Huang","year":"2012","journal-title":"Brain Behav."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1007\/s12031-014-0280-0","article-title":"Induction of Matrix Metalloproteinase-3 (MMP-3) Expression in the Microglia by Lipopolysaccharide (LPS) via Upregulation of Glycoprotein Nonmetastatic Melanoma B (GPNMB) Expression","volume":"54","author":"Shi","year":"2014","journal-title":"J. Mol. Neurosci."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"1878","DOI":"10.2353\/ajpath.2010.090950","article-title":"Novel Proteins Regulated by mTOR in Subependymal Giant Cell Astrocytomas of Patients with Tuberous Sclerosis Complex and New Therapeutic Implications","volume":"176","author":"Tyburczy","year":"2010","journal-title":"Am. J. Pathol."},{"key":"ref_176","doi-asserted-by":"crossref","unstructured":"Szulzewsky, F., Pelz, A., Feng, X., Synowitz, M., Markovic, D., Langmann, T., Holtman, I.R., Wang, X., Eggen, B.J.L., and Boddeke, H.W.G.M. (2015). Glioma-Associated Microglia\/Macrophages Display an Expression Profile Different from M1 and M2 Polarization and Highly Express Gpnmb and Spp1. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0116644"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"314","DOI":"10.3389\/fonc.2018.00314","article-title":"Glioblastoma Recurrence Correlates With Increased APE1 and Polarization Toward an Immuno-Suppressive Microenvironment","volume":"8","author":"Hudson","year":"2018","journal-title":"Front. Oncol."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"1970","DOI":"10.1158\/1078-0432.CCR-05-2797","article-title":"Glycoprotein Nonmetastatic Melanoma Protein B, a Potential Molecular Therapeutic Target in Patients with Glioblastoma Multiforme","volume":"12","author":"Kuan","year":"2006","journal-title":"Clin. Cancer Res."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1038\/srep00573","article-title":"The potential of GPNMB as novel neuroprotective factor in amyotrophic lateral sclerosis","volume":"2","author":"Tanaka","year":"2012","journal-title":"Sci. Rep."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.neuroscience.2014.06.065","article-title":"Glycoprotein nonmetastatic melanoma protein B (GPNMB) as a novel neuroprotective factor in cerebral ischemia\u2013reperfusion injury","volume":"277","author":"Nakano","year":"2014","journal-title":"Neuroscience"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"5167","DOI":"10.1007\/s12035-017-0707-z","article-title":"Glycoprotein NMB: An Emerging Role in Neurodegenerative Disease","volume":"55","author":"Budge","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1186\/s40478-018-0612-3","article-title":"Glycoprotein NMB: A novel Alzheimer\u2019s disease associated marker expressed in a subset of activated microglia","volume":"6","author":"Ogorek","year":"2018","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1186\/s12974-018-1100-1","article-title":"The glycoprotein GPNMB attenuates astrocyte inflammatory responses through the CD44 receptor","volume":"15","author":"Neal","year":"2018","journal-title":"J. Neuroinflammation"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.nbd.2018.08.013","article-title":"The glycoprotein GPNMB is selectively elevated in the substantia nigra of Parkinson\u2019s disease patients and increases after lysosomal stress","volume":"120","author":"Moloney","year":"2018","journal-title":"Neurobiol. Dis."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/j.immuni.2017.08.008","article-title":"The TREM2-APOE Pathway Drives the Transcriptional Phenotype of Dysfunctional Microglia in Neurodegenerative Diseases","volume":"47","author":"Krasemann","year":"2017","journal-title":"Immunity"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1016\/S1474-4422(12)70190-4","article-title":"The link between the GBA gene and parkinsonism","volume":"11","author":"Sidransky","year":"2012","journal-title":"Lancet. Neurol."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1111\/j.1471-4159.2008.05385.x","article-title":"Neuronal pigmented autophagic vacuoles: Lipofuscin, neuromelanin, and ceroid as macroautophagic responses during aging and disease","volume":"106","author":"Sulzer","year":"2008","journal-title":"J. Neurochem."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.mcn.2015.02.009","article-title":"The endosomal pathway in Parkinson\u2019s disease","volume":"66","author":"Perrett","year":"2015","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1016\/S2468-1253(17)30052-3","article-title":"Wolman\u2019s disease and cholesteryl ester storage disorder: The phenotypic spectrum of lysosomal acid lipase deficiency","volume":"2","author":"Pericleous","year":"2017","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1016\/S0168-8278(99)80356-0","article-title":"Hepatosplenomegalic lipidosis: What unless Gaucher? Adult cholesteryl ester storage disease (CESD) with anemia, mesenteric lipodystrophy, increased plasma chitotriosidase activity and a homozygous lysosomal acid lipase \u22121 exon 8 splice junction mutation","volume":"31","author":"Harzer","year":"1999","journal-title":"J. Hepatol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/1\/66\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:35:57Z","timestamp":1760196957000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/1\/66"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,12,24]]},"references-count":190,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,1]]}},"alternative-id":["ijms20010066"],"URL":"https:\/\/doi.org\/10.3390\/ijms20010066","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,12,24]]}}}