{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T01:52:29Z","timestamp":1781747549163,"version":"3.54.5"},"reference-count":107,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T00:00:00Z","timestamp":1781568000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health","award":["1R01NS138271"],"award-info":[{"award-number":["1R01NS138271"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Glycosylation, glycogen metabolism, and ubiquitination represent three fundamental cellular processes that are traditionally studied as distinct aspects of biology. Glycosylation and glycogen metabolism are unique carbohydrate-based pathways. The process of glycosylation generates structurally diverse glycans that regulate protein folding, cell signaling, and host\u2013pathogen interactions, while glycogen serves as a glucose reserve essential for energy homeostasis. Emerging evidence reveals a deep mechanistic connection between these pathways, particularly in the context of brain biology and inherited metabolic diseases. Here, we present recent research linking glycosylation defects with glycogen metabolism, highlighting how changes in the shared metabolites and enzymatic pathways contribute to human health and disease. We then discuss the overlapping disease symptoms of congenital disorders of glycosylation and glycogen storage diseases, with particular emphasis on polyglucosan body-forming diseases. We also highlight the role of non-canonical ubiquitin ligase complexes such as laforin\u2013malin and LUBAC and present emerging evidence for their potential role in the glycogen quality-control mechanism. Finally, we review current therapeutic strategies for CDGs and GSDs, including monosaccharide supplementation, glycogen synthase modulation, and gene therapy. Together, this review underscores glycogen as more than an energy store\u2014as a key contributor to glycosylation homeostasis and cellular regulation in health and disease.<\/jats:p>","DOI":"10.3390\/biom16060885","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:49:42Z","timestamp":1781743782000},"page":"885","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Glycogen and Glycosylation: Friends or Foes?"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3495-7068","authenticated-orcid":false,"given":"Rohit Sai Reddy","family":"Konada","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Division of Neurology, UT Southwestern Medical Center, Dallas, TX 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Osborn","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Neurology, UT Southwestern Medical Center, Dallas, TX 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7259-1482","authenticated-orcid":false,"given":"Sharmistha","family":"Mitra","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Neurology, UT Southwestern Medical Center, Dallas, TX 75390, USA"},{"name":"Department of Biochemistry, UT Southwestern Medical Center, Dallas, TX 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1038\/s41392-024-01886-1","article-title":"Glycosylation: Mechanisms, biological functions and clinical implications","volume":"9","author":"He","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1038\/s41581-019-0129-4","article-title":"Glycosylation in health and disease","volume":"15","author":"Reily","year":"2019","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1038\/s41580-020-00294-x","article-title":"Global view of human protein glycosylation pathways and functions","volume":"21","author":"Schjoldager","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1093\/glycob\/cww086","article-title":"Biological roles of glycans","volume":"27","author":"Varki","year":"2017","journal-title":"Glycobiology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"8256","DOI":"10.1073\/pnas.0801340105","article-title":"Effect of glycosylation on protein folding: A close look at thermodynamic stabilization","volume":"105","author":"Levy","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1038\/s41589-024-01748-5","article-title":"Fucosylation of glycoproteins and glycolipids: Opposing roles in cholera intoxication","volume":"21","author":"Ghorashi","year":"2025","journal-title":"Nat. Chem. Biol."},{"key":"ref_7","unstructured":"Varki, A., Cummings, R.D., Esko, J.D., Stanley, P., Hart, G.W., Aebi, M., Mohnen, D., Kinoshita, T., Packer, N.H., and Prestegard, J.H. (2026, May 07). Monosaccharide Diversity, Essentials of Glycobiology, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK579981\/."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3109","DOI":"10.1016\/j.cell.2021.04.023","article-title":"Small RNAs are modified with N-glycans and displayed on the surface of living cells","volume":"184","author":"Flynn","year":"2021","journal-title":"Cell"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3183","DOI":"10.1016\/j.jmb.2016.02.030","article-title":"Glycosylation Quality Control by the Golgi Structure","volume":"428","author":"Zhang","year":"2016","journal-title":"J. Mol. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1016\/j.tig.2018.03.002","article-title":"Perspectives on Glycosylation and Its Congenital Disorders","volume":"34","author":"Ng","year":"2018","journal-title":"Trends Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s44162-022-00003-6","article-title":"Epidemiology of congenital disorders of glycosylation (CDG)\u2014Overview and perspectives","volume":"1","author":"Piedade","year":"2022","journal-title":"J. Rare Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1038\/s41572-023-00456-z","article-title":"Glycogen storage diseases","volume":"9","author":"Hannah","year":"2023","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"4219","DOI":"10.1021\/jo050278f","article-title":"Protein Glycosylation:\u2009 New Challenges and Opportunities","volume":"70","author":"Wong","year":"2005","journal-title":"J. Org. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Mohanty, S., Chaudhary, B.P., and Zoetewey, D. (2020). Structural Insight into the Mechanism of N-Linked Glycosylation by Oligosaccharyltransferase. Biomolecules, 10.","DOI":"10.3390\/biom10040624"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2430","DOI":"10.1016\/j.bbamcr.2013.04.001","article-title":"N-linked protein glycosylation in the ER","volume":"1833","author":"Aebi","year":"2013","journal-title":"Biochim. Biophys. Acta (BBA)-Mol. Cell Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1038\/nrm3383","article-title":"Vertebrate protein glycosylation: Diversity, synthesis and function","volume":"13","author":"Moremen","year":"2012","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.semcdb.2014.11.005","article-title":"Cotranslational and posttranslocational N-glycosylation of proteins in the endoplasmic reticulum","volume":"41","author":"Shrimal","year":"2015","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_18","first-page":"11","article-title":"Chapter Two\u2014Glycans and Cancer: Role of N-Glycans in Cancer Biomarker, Progression and Metastasis, and Therapeutics","volume":"Volume 126","author":"Drake","year":"2015","journal-title":"Advances in Cancer Research"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Harada, Y., Ohkawa, Y., Kizuka, Y., and Taniguchi, N. (2019). Oligosaccharyltransferase: A Gatekeeper of Health and Tumor Progression. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20236074"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1038\/nrm1050","article-title":"Mannose 6-phosphate receptors: New twists in the tale","volume":"4","author":"Ghosh","year":"2003","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"BSR20220094","DOI":"10.1042\/BSR20220094","article-title":"O-glycosylation and its role in therapeutic proteins","volume":"42","author":"Thompson","year":"2022","journal-title":"Biosci. Rep."},{"key":"ref_22","first-page":"715","article-title":"Genetics of glycosylation in mammalian development and disease","volume":"25","author":"Stanley","year":"2024","journal-title":"Nat. Rev. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1186\/s13023-023-02879-z","article-title":"Congenital disorders of glycosylation (CDG): State of the art in 2022","volume":"18","author":"Francisco","year":"2023","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Paprocka, J., Jezela-Stanek, A., Tylki-Szyma\u0144ska, A., and Grunewald, S. (2021). Congenital Disorders of Glycosylation from a Neurological Perspective. Brain Sci., 11.","DOI":"10.3390\/brainsci11010088"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1042\/BST20180330","article-title":"Understanding cellular glycan surfaces in the central nervous system","volume":"47","author":"Iqbal","year":"2018","journal-title":"Biochem. Soc. Trans."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1016\/j.cmet.2021.05.003","article-title":"Brain glycogen serves as a critical glucosamine cache required for protein glycosylation","volume":"33","author":"Sun","year":"2021","journal-title":"Cell Metab."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e00049-20","DOI":"10.1128\/AEM.00049-20","article-title":"Bacterial Glycogen Provides Short-Term Benefits in Changing Environments","volume":"86","author":"Sekar","year":"2020","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Obel, L.F., Muller, M.S., Walls, A.B., Sickmann, H.M., Bak, L.K., Waagepetersen, H.S., and Schousboe, A. (2012). Brain glycogen-new perspectives on its metabolic function and regulation at the subcellular level. Front. Neuroenergetics, 4.","DOI":"10.3389\/fnene.2012.00003"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1002\/glia.23020","article-title":"Glycogen distribution in the microwave-fixed mouse brain reveals heterogeneous astrocytic patterns","volume":"64","author":"Oe","year":"2016","journal-title":"Glia"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e00446","DOI":"10.1016\/j.neurot.2024.e00446","article-title":"Neurological glycogen storage diseases and emerging therapeutics","volume":"21","author":"Colpaert","year":"2024","journal-title":"Neurotherapeutics"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1111\/jnc.15926","article-title":"The multifaceted roles of the brain glycogen","volume":"168","author":"Markussen","year":"2024","journal-title":"J. Neurochem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1038\/jcbfm.2014.33","article-title":"Neurons have an active glycogen metabolism that contributes to tolerance to hypoxia","volume":"34","author":"Saez","year":"2014","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1007\/s12035-019-01842-z","article-title":"Reactive Glia-Derived Neuroinflammation: A Novel Hallmark in Lafora Progressive Myoclonus Epilepsy That Progresses with Age","volume":"57","author":"Lahuerta","year":"2020","journal-title":"Mol. Neurobiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1007\/978-1-0716-4284-9_13","article-title":"Large-Scale Protein Production and Activity Assay Protocols for Human Glycogen Synthase-Glycogenin Complex","volume":"2882","author":"Marr","year":"2025","journal-title":"Methods Mol. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.cmet.2011.01.017","article-title":"Phosphate incorporation during glycogen synthesis and Lafora disease","volume":"13","author":"Tagliabracci","year":"2011","journal-title":"Cell Metab."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.bbacli.2016.02.001","article-title":"Glycogen metabolism in humans","volume":"5","year":"2016","journal-title":"BBA Clin."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"102093","DOI":"10.1016\/j.jbc.2022.102093","article-title":"Glycogen-autophagy: Molecular machinery and cellular mechanisms of glycophagy","volume":"298","author":"Koutsifeli","year":"2022","journal-title":"J. Biol. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"19262","DOI":"10.1073\/pnas.0707952104","article-title":"Laforin is a glycogen phosphatase, deficiency of which leads to elevated phosphorylation of glycogen in vivo","volume":"104","author":"Tagliabracci","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"dmm049802","DOI":"10.1242\/dmm.049802","article-title":"Laforin targets malin to glycogen in Lafora progressive myoclonus epilepsy","volume":"16","author":"Mitra","year":"2023","journal-title":"Dis. Models Mech."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"4069","DOI":"10.1074\/jbc.M708712200","article-title":"Malin Decreases Glycogen Accumulation by Promoting the Degradation of Protein Targeting to Glycogen (PTG)","volume":"283","author":"Worby","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1038\/2470","article-title":"Mutations in a gene encoding a novel protein tyrosine phosphatase cause progressive myoclonus epilepsy","volume":"20","author":"Minassian","year":"1998","journal-title":"Nat. Genet."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.neurol.2021.06.006","article-title":"Lafora disease: Current biology and therapeutic approaches","volume":"178","author":"Mitra","year":"2022","journal-title":"Rev. Neurol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1604","DOI":"10.1093\/hmg\/ddr598","article-title":"Laforin and malin knockout mice have normal glucose disposal and insulin sensitivity","volume":"21","author":"Segvich","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2443","DOI":"10.1042\/BST20210838","article-title":"LUBAC: A new player in polyglucosan body disease","volume":"49","author":"Aboujaoude","year":"2021","journal-title":"Biochem. Soc. Trans."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1007\/s00401-024-02698-x","article-title":"Myofiber-type-dependent \u2018boulder\u2019 or \u2018multitudinous pebble\u2019 formations across distinct amylopectinoses","volume":"147","author":"Mitra","year":"2024","journal-title":"Acta Neuropathol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2361","DOI":"10.1093\/brain\/awac017","article-title":"Glycogen synthase downregulation rescues the amylopectinosis of murine RBCK1 deficiency","volume":"145","author":"Nitschke","year":"2022","journal-title":"Brain"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e109700","DOI":"10.15252\/embj.2021109700","article-title":"HOIL-1 ubiquitin ligase activity targets unbranched glucosaccharides and is required to prevent polyglucosan accumulation","volume":"41","author":"Kelsall","year":"2022","journal-title":"EMBO J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e2214227119","DOI":"10.1073\/pnas.2214227119","article-title":"HOIP modulates the stability of GPx4 by linear ubiquitination","volume":"119","author":"Dong","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"13293","DOI":"10.1073\/pnas.1905873116","article-title":"The E3 ligase HOIL-1 catalyses ester bond formation between ubiquitin and components of the Myddosome in mammalian cells","volume":"116","author":"Kelsall","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1002\/jimd.12234","article-title":"RBCK1-related disease: A rare multisystem disorder with polyglucosan storage, auto-inflammation, recurrent infections, skeletal, and cardiac myopathy-Four additional patients and a review of the current literature","volume":"43","author":"Phadke","year":"2020","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e00416","DOI":"10.1042\/BSR20160385","article-title":"Liver glucose metabolism in humans","volume":"36","year":"2016","journal-title":"Biosci. Rep."},{"key":"ref_52","unstructured":"Varki, A., Cummings, R.D., Esko, J.D., Stanley, P., Hart, G.W., Aebi, M., Mohnen, D., Kinoshita, T., Packer, N.H., and Prestegard, J.H. (2026, May 07). Glycosylation Precursors, Essentials of Glycobiology, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK579932\/."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1007\/s12253-018-0446-0","article-title":"The ER\u2014Glycogen Particle\u2014Phagophore Triangle: A Hub Connecting Glycogenolysis and Glycophagy?","volume":"24","author":"Mandl","year":"2018","journal-title":"Pathol. Oncol. Res."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Mandl, J. (2023). Glycogen\u2014Endoplasmic Reticulum Connection in the Liver. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24021074"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.mam.2015.08.006","article-title":"Polyglucosan storage myopathies","volume":"46","author":"Oldfors","year":"2015","journal-title":"Mol. Asp. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1097\/WCO.0000000000000484","article-title":"Update on new muscle glycogenosis","volume":"30","author":"Laforet","year":"2017","journal-title":"Curr. Opin. Neurol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1002\/jimd.12654","article-title":"Gene therapy for glycogen storage diseases","volume":"47","author":"Koeberl","year":"2024","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Xiao, R., Zheng, J., Loponte, H.F.B.R., Ding, Y., Gross-Valle, C., Derks, T.G.J., Horvatovich, P.L., Heiner-Fokkema, M.R., Bakker, B.M., and Wolters, J.C. (2025). Decoding the Glycan Signature: Unraveling N-Glycosylation Alterations in Glycogen Storage Disease Ia and Ib. bioRxiv.","DOI":"10.1101\/2025.10.23.684118"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1016\/j.ajhg.2021.04.013","article-title":"A mutation in SLC37A4 causes a dominantly inherited congenital disorder of glycosylation characterized by liver dysfunction","volume":"108","author":"Ng","year":"2021","journal-title":"Am. J. Hum. Genet."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.metabol.2018.01.004","article-title":"Aberrant apolipoprotein C-III glycosylation in glycogen storage disease type III and IX","volume":"82","author":"Ondruskova","year":"2018","journal-title":"Metabolism"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1093\/glycob\/cwr023","article-title":"G6PC3 mutations are associated with a major defect of glycosylation: A novel mechanism for neutrophil dysfunction","volume":"21","author":"Hayee","year":"2011","journal-title":"Glycobiology"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"3115","DOI":"10.1016\/j.molcel.2024.07.013","article-title":"Sugar-mediated non-canonical ubiquitination impairs Nrf1\/NFE2L1 activation","volume":"84","author":"Yoshida","year":"2024","journal-title":"Mol. Cell"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Jochem, M., Cobbold, S.A., Goodman, C.A., Kueng, C., Cerra, A., Fielden, L.F., Kim, M.L., Schenk, P., Agarwal, R., and Wang, X.S. (2026). Ubiquitination of glycogen and metabolites in cells and tissues. Nature.","DOI":"10.1038\/s41586-026-10548-x"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/0014-5793(86)80041-2","article-title":"Glucosamine is a normal component of liver glycogen","volume":"194","author":"Kirkman","year":"1986","journal-title":"FEBS Lett."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1038\/cr.2016.39","article-title":"Ubiquitin modifications","volume":"26","author":"Swatek","year":"2016","journal-title":"Cell Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1042\/BST20253029","article-title":"Insights into non-proteinaceous ubiquitination","volume":"53","author":"Dearlove","year":"2025","journal-title":"Biochem. Soc. Trans."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1016\/j.cmet.2019.07.002","article-title":"Targeting Pathogenic Lafora Bodies in Lafora Disease Using an Antibody-Enzyme Fusion","volume":"30","author":"Brewer","year":"2019","journal-title":"Cell Metab."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1002\/ana.23963","article-title":"Polyglucosan body myopathy caused by defective ubiquitin ligase RBCK1","volume":"74","author":"Nilsson","year":"2013","journal-title":"Ann. Neurol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1084\/jem.20141130","article-title":"Human HOIP and LUBAC deficiency underlies autoinflammation, immunodeficiency, amylopectinosis, and lymphangiectasia","volume":"212","author":"Boisson","year":"2015","journal-title":"J. Exp. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1919","DOI":"10.1093\/hmg\/ddz032","article-title":"Cardiomyopathy with lethal arrhythmias associated with inactivation of KLHL24","volume":"28","author":"Abramsson","year":"2019","journal-title":"Hum. Mol. Genet."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"e170","DOI":"10.1111\/epi.17634","article-title":"IRF2BPL as a novel causative gene for progressive myoclonus epilepsy","volume":"64","author":"Gardella","year":"2023","journal-title":"Epilepsia"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Abu Bakar, N., and Hamzan, N.I. (2025). Advancement in Clinical Glycomics and Glycoproteomics for Congenital Disorders of Glycosylation: Progress and Challenges Ahead. Biomedicines, 13.","DOI":"10.20944\/preprints202506.0411.v1"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1007\/s00431-017-2852-9","article-title":"The ethical framework for performing research with rare inherited neurometabolic disease patients","volume":"176","author":"Giannuzzi","year":"2017","journal-title":"Eur. J. Pediatr."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"108567","DOI":"10.1016\/j.ymgme.2024.108567","article-title":"Treatment of congenital disorders of glycosylation: An overview","volume":"143","author":"Quelhas","year":"2024","journal-title":"Mol. Genet. Metab."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Park, J.H., and Marquardt, T. (2021). Treatment Options in Congenital Disorders of Glycosylation. Front. Genet., 12.","DOI":"10.3389\/fgene.2021.735348"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"108488","DOI":"10.1016\/j.ymgme.2024.108488","article-title":"D-mannose as a new therapy for fucokinase deficiency-related congenital disorder of glycosylation (FCSK-CDG)","volume":"142","author":"Starosta","year":"2024","journal-title":"Mol. Genet. Metab."},{"key":"ref_77","first-page":"3976","article-title":"Correction of leukocyte adhesion deficiency type II with oral fucose","volume":"94","author":"Marquardt","year":"1999","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1186\/s13023-020-01528-z","article-title":"Dietary mannose supplementation in phosphomannomutase 2 deficiency (PMM2-CDG)","volume":"15","author":"Taday","year":"2020","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.ajhg.2013.10.024","article-title":"Solving Glycosylation Disorders: Fundamental Approaches Reveal Complicated Pathways","volume":"94","author":"Freeze","year":"2014","journal-title":"Am. J. Hum. Genet."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1038\/s41436-020-0767-8","article-title":"Clinical and biochemical improvement with galactose supplementation in SLC35A2-CDG","volume":"22","author":"Witters","year":"2020","journal-title":"Genet. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1007\/s13311-022-01218-7","article-title":"AAV-Mediated Artificial miRNA Reduces Pathogenic Polyglucosan Bodies and Neuroinflammation in Adult Polyglucosan Body and Lafora Disease Mouse Models","volume":"19","author":"Gumusgoz","year":"2022","journal-title":"Neurotherapeutics"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2985","DOI":"10.1093\/brain\/awab194","article-title":"Gys1 antisense therapy rescues neuropathological bases of murine Lafora disease","volume":"144","author":"Ahonen","year":"2021","journal-title":"Brain"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.1007\/s13311-021-01040-7","article-title":"Targeting Gys1 with AAV-SaCas9 Decreases Pathogenic Polyglucosan Bodies and Neuroinflammation in Adult Polyglucosan Body and Lafora Disease Mouse Models","volume":"18","author":"Gumusgoz","year":"2021","journal-title":"Neurotherapeutics"},{"key":"ref_84","unstructured":"Duan, D. (2011). Lentiviral Vector Delivery of shRNA into Cultured Primary Myogenic Cells: A Tool for Therapeutic Target Validation. Muscle Gene Therapy: Methods and Protocols, Humana Press."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"eadf1691","DOI":"10.1126\/scitranslmed.adf1691","article-title":"Small-molecule inhibition of glycogen synthase 1 for the treatment of Pompe disease and other glycogen storage disorders","volume":"16","author":"Ullman","year":"2024","journal-title":"Sci. Transl. Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"117621","DOI":"10.1016\/j.ejmech.2025.117621","article-title":"Discovery of novel PI3KC2gamma inhibitors with high potency, selectivity, and favorable pharmacokinetics for glycogen metabolism regulation","volume":"291","author":"Zhong","year":"2025","journal-title":"Eur. J. Med. Chem."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"e70514","DOI":"10.1002\/ctm2.70514","article-title":"Advances in gene therapy for Lafora disease: Intravenous recombinant adeno-associated virus-mediated delivery of EPM2A and EPM2B genes","volume":"15","author":"Sciaccaluga","year":"2025","journal-title":"Clin. Transl. Med."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"e00866","DOI":"10.1016\/j.neurot.2026.e00866","article-title":"Lafora disease gene therapy: EPM2A but not EPM2B overexpression results in Lafora body formation","volume":"23","author":"Alao","year":"2026","journal-title":"Neurotherapeutics"},{"key":"ref_89","unstructured":"ClinicalTrials.gov (2026, June 10). A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Adeno-Associated Virus Serotype 8-Mediated Gene Transfer of Glucose-6-Phosphatase in Patients with Glycogen Storage Disease Type Ia (NCT05139316), Available online: https:\/\/clinicaltrials.gov\/study\/NCT05139316."},{"key":"ref_90","unstructured":"ClinicalTrials.gov (2026, June 10). Single Arm, Multicenter, Open and Dose-escalation Clinical Study on Safety, Tolerance, and Efficacy of GC301, an AAV-Delivered Gene Transfer Therapy in Patients with Infantile-Onset Pompe Disease (NCT05567627), Available online: https:\/\/clinicaltrials.gov\/study\/NCT05567627."},{"key":"ref_91","unstructured":"ClinicalTrials.gov (2026, June 10). A Phase 1\/2, Open-Label, Ascending-Dose Clinical Study to Evaluate the Safety and Preliminary Efficacy of AT845, an AAV8-Delivered Gene Transfer Therapy in Patients with Late Onset Pompe Disease (NCT04174105), Available online: https:\/\/clinicaltrials.gov\/study\/NCT04174105."},{"key":"ref_92","unstructured":"ClinicalTrials.gov (2026, June 10). Phase 1\/2, Dose-Escalation Study to Evaluate the Safety, Tolerability and Efficacy of a Single Intravenous Infusion of SPK-3006 in Adults with Late-Onset Pompe Disease (NCT04093349), Available online: https:\/\/clinicaltrials.gov\/study\/NCT04093349."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"108590","DOI":"10.1016\/j.ymgme.2024.108590","article-title":"Pompe disease: Unmet needs and emerging therapies","volume":"143","author":"George","year":"2024","journal-title":"Mol. Genet. Metab."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1097\/WCO.0000000000001385","article-title":"Enzyme replacement therapies in adults with Pompe disease: From trials to real-world data","volume":"38","author":"Potters","year":"2025","journal-title":"Curr. Opin. Neurol."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Noebels, J.L., Avoli, M., Rogawski, M.A., Vezzani, A., and Delgado-Escueta, A.V. (2024). Treating Lafora Disease with an Antibody-Enzyme Fusion. Jasper\u2019s Basic Mechanisms of the Epilepsies, Oxford University Press. [5th ed.].","DOI":"10.1093\/med\/9780197549469.001.0001"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1016\/j.molmed.2019.08.005","article-title":"Antibody-Mediated Enzyme Therapeutics and Applications in Glycogen Storage Diseases","volume":"25","author":"Zhou","year":"2019","journal-title":"Trends Mol. Med."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1038\/gim.2017.106","article-title":"SLC39A8 deficiency: Biochemical correction and major clinical improvement by manganese therapy","volume":"20","author":"Park","year":"2018","journal-title":"Genet. Med."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1002\/ana.25457","article-title":"AZATAX: Acetazolamide safety and efficacy in cerebellar syndrome in PMM2 congenital disorder of glycosylation (PMM2-CDG)","volume":"85","author":"Bolasell","year":"2019","journal-title":"Ann. Neurol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"2365","DOI":"10.1212\/WNL.0000000000004711","article-title":"Long-term benefit of enzyme replacement therapy in Pompe disease: A 5-year prospective study","volume":"89","author":"Kuperus","year":"2017","journal-title":"Neurology"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1089\/hum.2008.010","article-title":"Ability of adeno-associated virus serotype 8-mediated hepatic expression of acid alpha-glucosidase to correct the biochemical and motor function deficits of presymptomatic and symptomatic Pompe mice","volume":"19","author":"Ziegler","year":"2008","journal-title":"Hum. Gene Ther."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1016\/j.ymthe.2017.12.019","article-title":"Rescue of GSDIII Phenotype with Gene Transfer Requires Liver- and Muscle-Targeted GDE Expression","volume":"26","author":"Vidal","year":"2018","journal-title":"Mol. Ther."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.omtm.2020.05.034","article-title":"A Novel Gene Therapy Approach for GSD III Using an AAV Vector Encoding a Bacterial Glycogen Debranching Enzyme","volume":"18","author":"Lim","year":"2020","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1089\/hum.2016.099","article-title":"Systemic Correction of Murine Glycogen Storage Disease Type IV by an AAV-Mediated Gene Therapy","volume":"28","author":"Yi","year":"2017","journal-title":"Hum. Gene Ther."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1093\/hmg\/ddz214","article-title":"Systemic AAV8-mediated delivery of a functional copy of muscle glycogen phosphorylase (Pygm) ameliorates disease in a murine model of McArdle disease","volume":"29","author":"McNamara","year":"2020","journal-title":"Hum. Mol. Genet."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.nmd.2007.10.006","article-title":"Adenovirus and adeno-associated virus-mediated delivery of human myophosphorylase cDNA and LacZ cDNA to muscle in the ovine model of McArdle\u2019s disease: Expression and re-expression of glycogen phosphorylase","volume":"18","author":"Howell","year":"2008","journal-title":"Neuromuscul. Disord."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.nmd.2013.10.003","article-title":"Phosphorylase re-expression, increase in the force of contraction and decreased fatigue following notexin-induced muscle damage and regeneration in the ovine model of McArdle disease","volume":"24","author":"Howell","year":"2014","journal-title":"Neuromuscul. Disord."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Sanz, P., Serratosa, J.M., and Sanchez, M.P. (2021). Beneficial Effects of Metformin on the Central Nervous System, with a Focus on Epilepsy and Lafora Disease. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22105351"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/6\/885\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T01:18:36Z","timestamp":1781745516000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/6\/885"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,16]]},"references-count":107,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["biom16060885"],"URL":"https:\/\/doi.org\/10.3390\/biom16060885","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,16]]}}}