{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,13]],"date-time":"2026-11-13T04:38:21Z","timestamp":1794544701814,"version":"4.9.1"},"reference-count":50,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["10.55776\/P35532"],"award-info":[{"award-number":["10.55776\/P35532"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["10.55776\/J4932"],"award-info":[{"award-number":["10.55776\/J4932"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["10.55776\/ESP2877024"],"award-info":[{"award-number":["10.55776\/ESP2877024"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["10.55776\/PAT3403323"],"award-info":[{"award-number":["10.55776\/PAT3403323"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["10.55776\/F73"],"award-info":[{"award-number":["10.55776\/F73"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004410","name":"European Molecular Biology Organization","doi-asserted-by":"publisher","award":["11929"],"award-info":[{"award-number":["11929"]}],"id":[{"id":"10.13039\/100004410","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Batten Disease Global Research Initiative (BDGRI) and NCL Foundation (NCL-Stiftung)."}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Cell Biol"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    According to text book knowledge, de novo glycerophospholipid (GPL) synthesis begins with the acylation of glycerol-3-phosphate to form phosphatidic acid, the precursor of all other GPLs. Here we describe an alternative GPL synthesis pathway that starts with the acyl-CoA-dependent acylation of glycerophosphoglycerol, resulting in the formation of lysophosphatidylglycerol. The acyltransferase reaction is catalysed by the Batten disease-associated protein ceroid lipofuscinosis neuronal 8 (CLN8). Tracer studies revealed that CLN8-derived lysophosphatidylglycerol is selectively converted into bis(monoacylglycero)phosphate (BMP), a GPL essential for lysosomal lipid homeostasis but not into phosphatidylglycerol or cardiolipin.\n                    <jats:italic>CLN8<\/jats:italic>\n                    -knockout cells and mice cannot utilize glycerophosphoglycerol for BMP synthesis, resulting in BMP deficiency and excess accumulation of phospholipids in lysosomes. The lipid synthesis pathway described herein is relevant for understanding lysosomal lipid metabolism and the pathogenesis of neurodegenerative diseases. BMP deficiency may contribute to or even underlie lysosomal cargo accumulation in certain forms of Batten disease and other lysosomal storage disorders.\n                  <\/jats:p>","DOI":"10.1038\/s41556-026-02059-8","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T09:03:18Z","timestamp":1789462998000},"page":"2078-2087","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Batten disease protein CLN8 enables a non-canonical phospholipid synthesis pathway"],"prefix":"10.1038","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4804-1341","authenticated-orcid":false,"given":"Johannes","family":"Breithofer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2376-947X","authenticated-orcid":false,"given":"Nermeen","family":"Fawzy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Zitta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Tischitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7628-7368","authenticated-orcid":false,"given":"Dominik","family":"Bulfon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9891-7149","authenticated-orcid":false,"given":"Clemens","family":"Hofmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2905-6476","authenticated-orcid":false,"given":"Lennart","family":"Hartig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0146-702X","authenticated-orcid":false,"given":"Carina","family":"Wagner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7110-9957","authenticated-orcid":false,"given":"Gernot F.","family":"Grabner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Pirchheim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8190-7151","authenticated-orcid":false,"given":"Achim","family":"Lass","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9000-1602","authenticated-orcid":false,"given":"Ulrike","family":"Taschler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keira","family":"Turner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2295-6065","authenticated-orcid":false,"given":"Kasparas","family":"Petkevicius","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2500-3585","authenticated-orcid":false,"given":"Ulrich","family":"Stelzl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1357-7573","authenticated-orcid":false,"given":"Dagmar","family":"Kratky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6009-7359","authenticated-orcid":false,"given":"Rolf","family":"Breinbauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7354-870X","authenticated-orcid":false,"given":"Robert","family":"Zimmermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"2059_CR1","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1038\/32440","volume":"392","author":"T Kobayashi","year":"1998","unstructured":"Kobayashi, T. et al. A lipid associated with the antiphospholipid syndrome regulates endosome structure and function. Nature 392, 193\u2013197 (1998).","journal-title":"Nature"},{"key":"2059_CR2","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1038\/s41586-025-08942-y","volume":"642","author":"K Nyame","year":"2025","unstructured":"Nyame, K. et al. PLA2G15 is a BMP hydrolase and its targeting ameliorates lysosomal disease. Nature 642, 474\u2013483 (2025).","journal-title":"Nature"},{"key":"2059_CR3","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1126\/science.1092425","volume":"303","author":"H Matsuo","year":"2004","unstructured":"Matsuo, H. et al. Role of LBPA and Alix in multivesicular liposome formation and endosome organization. Science 303, 531\u2013534 (2004).","journal-title":"Science"},{"key":"2059_CR4","doi-asserted-by":"publisher","first-page":"1594","DOI":"10.1007\/s11064-010-0337-6","volume":"36","author":"HD Gallala","year":"2011","unstructured":"Gallala, H. D. & Sandhoff, K. Biological function of the cellular lipid BMP\u2014BMP as a key activator for cholesterol sorting and membrane digestion. Neurochem. Res. 36, 1594\u20131600 (2011).","journal-title":"Neurochem. Res."},{"key":"2059_CR5","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1146\/annurev-biochem-092823-113814","volume":"93","author":"UN Medoh","year":"2024","unstructured":"Medoh, U. N. & Abu-Remaileh, M. The Bis(monoacylglycero)-phosphate hypothesis: from lysosomal function to therapeutic avenues. Annu. Rev. Biochem. 93, 447\u2013469 (2024).","journal-title":"Annu. Rev. Biochem."},{"key":"2059_CR6","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1002\/anie.201106470","volume":"51","author":"H Tan","year":"2012","unstructured":"Tan, H., Makino, A., Sudesh, K., Greimel, P. & Kobayashi, T. Spectroscopic evidence for the unusual stereochemical configuration of an endosome-specific lipid. Angew Chem. Int. Ed. 51, 533\u2013535 (2012).","journal-title":"Angew Chem. Int. Ed."},{"key":"2059_CR7","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1016\/0009-3084(74)90034-6","volume":"13","author":"J Brotherus","year":"1974","unstructured":"Brotherus, J., Renkonen, O., Herrmann, J. & Fischer, W. Novel stereoconfiguration in lyso-bis-phosphatidic acid of cultured BHK-cells. Chem. Phys. Lipids 13, 178\u2013182 (1974).","journal-title":"Chem. Phys. Lipids"},{"key":"2059_CR8","doi-asserted-by":"publisher","first-page":"13995","DOI":"10.1021\/bi961164o","volume":"35","author":"B Amidon","year":"1996","unstructured":"Amidon, B., Brown, A. & Waite, M. Transacylase and phospholipases in the synthesis of bis(monoacylglycero)phosphate. Biochemistry 35, 13995\u201314002 (1996).","journal-title":"Biochemistry"},{"key":"2059_CR9","doi-asserted-by":"publisher","first-page":"1182","DOI":"10.1126\/science.adg9288","volume":"381","author":"UN Medoh","year":"2023","unstructured":"Medoh, U. N. et al. The Batten disease gene product CLN5 is the lysosomal bis(monoacylglycero)phosphate synthase. Science 381, 1182\u20131189 (2023).","journal-title":"Science"},{"key":"2059_CR10","doi-asserted-by":"publisher","first-page":"6820","DOI":"10.1016\/j.cell.2024.09.036","volume":"187","author":"S Singh","year":"2024","unstructured":"Singh, S. et al. PLD3 and PLD4 synthesize S,S-BMP, a key phospholipid enabling lipid degradation in lysosomes. Cell 187, 6820\u20136834 (2024).","journal-title":"Cell"},{"key":"2059_CR11","doi-asserted-by":"publisher","first-page":"63","DOI":"10.3389\/fcell.2020.00063","volume":"8","author":"NJ Blunsom","year":"2020","unstructured":"Blunsom, N. J. & Cockcroft, S. CDP-diacylglycerol synthases (CDS): gateway to phosphatidylinositol and cardiolipin synthesis. Front. Cell Dev. Biol. 8, 63 (2020).","journal-title":"Front. Cell Dev. Biol."},{"key":"2059_CR12","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1002\/iub.337","volume":"62","author":"F Gibellini","year":"2010","unstructured":"Gibellini, F. & Smith, T. K. The Kennedy pathway\u2014de novo synthesis of phosphatidylethanolamine and phosphatidylcholine. IUBMB Life 62, 414\u2013428 (2010).","journal-title":"IUBMB Life"},{"key":"2059_CR13","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1038\/s41572-018-0025-4","volume":"4","author":"FM Platt","year":"2018","unstructured":"Platt, F. M., d\u2019Azzo, A., Davidson, B. L., Neufeld, E. F. & Tifft, C. J. Lysosomal storage diseases. Nat. Rev. Dis. Primers 4, 27 (2018).","journal-title":"Nat. Rev. Dis. Primers"},{"key":"2059_CR14","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1038\/13868","volume":"23","author":"S Ranta","year":"1999","unstructured":"Ranta, S. et al. The neuronal ceroid lipofuscinoses in human EPMR and mnd mutant mice are associated with mutations in CLN8. Nat. Genet. 23, 233\u2013236 (1999).","journal-title":"Nat. Genet."},{"key":"2059_CR15","doi-asserted-by":"publisher","first-page":"2237","DOI":"10.1016\/j.bbadis.2015.05.011","volume":"1852","author":"SE Mole","year":"2015","unstructured":"Mole, S. E. & Cotman, S. L. Genetics of the neuronal ceroid lipofuscinoses (Batten disease). Biochim. Biophys. Acta Mol. Basis Dis. 1852, 2237\u20132241 (2015).","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"2059_CR16","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1002\/humu.21624","volume":"33","author":"M Kousi","year":"2012","unstructured":"Kousi, M., Lehesjoki, A.-E. & Mole, S. E. Update of the mutation spectrum and clinical correlations of over 360 mutations in eight genes that underlie the neuronal ceroid lipofuscinoses. Hum. Mutat. 33, 42\u201363 (2012).","journal-title":"Hum. Mutat."},{"key":"2059_CR17","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1007\/s10930-024-10190-4","volume":"43","author":"SM Hejazian","year":"2024","unstructured":"Hejazian, S. M., Pirmoradi, S., Zununi Vahed, S., Kumar Roy, R. & Hosseiniyan Khatibi, S. M. An update on glycerophosphodiester phosphodiesterases; from bacteria to human. Protein J. 43, 187\u2013199 (2024).","journal-title":"Protein J."},{"key":"2059_CR18","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-54213-1","volume":"15","author":"D Bulfon","year":"2024","unstructured":"Bulfon, D. et al. Functionally overlapping intra- and extralysosomal pathways promote bis(monoacylglycero)phosphate synthesis in mammalian cells. Nat. Commun. 15, 9937 (2024).","journal-title":"Nat. Commun."},{"key":"2059_CR19","doi-asserted-by":"publisher","first-page":"24667","DOI":"10.1074\/jbc.M010793200","volume":"276","author":"J-H Kim","year":"2001","unstructured":"Kim, J.-H., Lewin, T. M. & Coleman, R. A. Expression and characterization of recombinant rat Acyl-CoA synthetases 1, 4, and 5. J. Biol. Chem. 276, 24667\u201324673 (2001).","journal-title":"J. Biol. Chem."},{"key":"2059_CR20","doi-asserted-by":"publisher","first-page":"17707","DOI":"10.1016\/S0021-9258(19)47429-2","volume":"266","author":"T Yoshimori","year":"1991","unstructured":"Yoshimori, T., Yamamoto, A., Moriyama, Y., Futai, M. & Tashiro, Y. Bafilomycin A1, a specific inhibitor of vacuolar-type H+-ATPase, inhibits acidification and protein degradation in lysosomes of cultured cells. J. Biol. Chem. 266, 17707\u201317712 (1991).","journal-title":"J. Biol. Chem."},{"key":"2059_CR21","doi-asserted-by":"publisher","first-page":"2079","DOI":"10.1194\/jlr.R800013-JLR200","volume":"49","author":"RE Gimeno","year":"2008","unstructured":"Gimeno, R. E. & Cao, J. Thematic review series: glycerolipids. Mammalian glycerol-3-phosphate acyltransferases: new genes for an old activity. J. Lipid Res. 49, 2079\u20132088 (2008).","journal-title":"J. Lipid Res."},{"key":"2059_CR22","doi-asserted-by":"publisher","first-page":"eadr3723","DOI":"10.1126\/sciadv.adr3723","volume":"11","author":"PK Sheokand","year":"2025","unstructured":"Sheokand, P. K. et al. TRAM-LAG1-CLN8 family proteins are acyltransferases regulating phospholipid composition. Sci. Adv. 11, eadr3723 (2025).","journal-title":"Sci. Adv."},{"key":"2059_CR23","doi-asserted-by":"publisher","first-page":"55866","DOI":"10.1074\/jbc.M406710200","volume":"279","author":"Y Yang","year":"2004","unstructured":"Yang, Y., Cao, J. & Shi, Y. Identification and characterization of a gene encoding human LPGAT1, an endoplasmic reticulum-associated lysophosphatidylglycerol acyltransferase. J. Biol. Chem. 279, 55866\u201355874 (2004).","journal-title":"J. Biol. Chem."},{"key":"2059_CR24","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1126\/science.aan6298","volume":"358","author":"M Abu-Remaileh","year":"2017","unstructured":"Abu-Remaileh, M. et al. Lysosomal metabolomics reveals V-ATPase- and mTOR-dependent regulation of amino acid efflux from lysosomes. Science 358, 807\u2013813 (2017).","journal-title":"Science"},{"key":"2059_CR25","doi-asserted-by":"publisher","first-page":"995","DOI":"10.1194\/jlr.RA119000516","volume":"61","author":"GF Grabner","year":"2020","unstructured":"Grabner, G. F. et al. Metabolic regulation of the lysosomal cofactor bis(monoacylglycero)phosphate in mice. J. Lipid Res. 61, 995\u20131003 (2020).","journal-title":"J. Lipid Res."},{"key":"2059_CR26","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1007\/BF00270037","volume":"97","author":"WJ Brown","year":"1992","unstructured":"Brown, W. J., Sullivan, T. R. & Greenspan, P. Nile red staining of lysosomal phospholipid inclusions. Histochemistry 97, 349\u2013354 (1992).","journal-title":"Histochemistry"},{"key":"2059_CR27","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1016\/S0022-2275(20)34307-8","volume":"26","author":"P Greenspan","year":"1985","unstructured":"Greenspan, P. & Fowler, S. D. Spectrofluorometric studies of the lipid probe, nile red. J. Lipid Res. 26, 781\u2013789 (1985).","journal-title":"J. Lipid Res."},{"key":"2059_CR28","doi-asserted-by":"publisher","first-page":"1792","DOI":"10.1038\/s42255-022-00706-6","volume":"4","author":"AM Hosios","year":"2022","unstructured":"Hosios, A. M. et al. mTORC1 regulates a lysosome-dependent adaptive shift in intracellular lipid species. Nat. Metab. 4, 1792\u20131811 (2022).","journal-title":"Nat. Metab."},{"key":"2059_CR29","doi-asserted-by":"publisher","first-page":"32157","DOI":"10.1074\/jbc.M202838200","volume":"277","author":"T Kobayashi","year":"2002","unstructured":"Kobayashi, T. et al. Separation and characterization of late endosomal membrane domains. J. Biol. Chem. 277, 32157\u201332164 (2002).","journal-title":"J. Biol. Chem."},{"key":"2059_CR30","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1006\/abio.2001.5158","volume":"296","author":"C Luquain","year":"2001","unstructured":"Luquain, C., Laugier, C., Lagarde, M. & Pageaux, J.-F. High-performance liquid chromatography determination of bis(monoacylglycerol) phosphate and other lysophospholipids. Anal. Biochem. 296, 41\u201348 (2001).","journal-title":"Anal. Biochem."},{"key":"2059_CR31","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1042\/bj3510795","volume":"351","author":"C Luquain","year":"2000","unstructured":"Luquain, C. et al. Bis(monoacylglycerol) phosphate in rat uterine stromal cells: structural characterization and specific esterification of docosahexaenoic acid. Biochem. J. 351, 795\u2013804 (2000).","journal-title":"Biochem. J."},{"key":"2059_CR32","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1194\/jlr.M800300-JLR200","volume":"50","author":"J Bouvier","year":"2009","unstructured":"Bouvier, J. et al. Selective decrease of bis(monoacylglycero)phosphate content in macrophages by high supplementation with docosahexaenoic acid. J. Lipid Res. 50, 243\u2013255 (2009).","journal-title":"J. Lipid Res."},{"key":"2059_CR33","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1002\/ana.410330408","volume":"33","author":"RT Bronson","year":"1993","unstructured":"Bronson, R. T., Lake, B. D., Cook, S., Taylor, S. & Davisson, M. T. Motor neuron degeneration of mice is a model of neuronal ceroid lipofuscinosis (Batten\u2019s disease). Ann. Neurol. 33, 381\u2013385 (1993).","journal-title":"Ann. Neurol."},{"key":"2059_CR34","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1038\/s41582-025-01132-4","volume":"21","author":"EA Zi\u00f3\u0142kowska","year":"2025","unstructured":"Zi\u00f3\u0142kowska, E. A. et al. Neuronal ceroid lipofuscinosis: underlying mechanisms and emerging therapeutic targets. Nat. Rev. Neurol. 21, 606\u2013622 (2025).","journal-title":"Nat. Rev. Neurol."},{"key":"2059_CR35","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1111\/j.1750-3639.2004.tb00077.x","volume":"14","author":"J Tyynel\u00e4","year":"2004","unstructured":"Tyynel\u00e4, J., Cooper, J. D., Khan, M. N., Shemilt, S. J. & Haltia, M. Hippocampal pathology in the human neuronal ceroid-lipofuscinoses: distinct patterns of storage deposition, neurodegeneration and glial activation. Brain Pathol. 14, 349\u2013357 (2004).","journal-title":"Brain Pathol."},{"key":"2059_CR36","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.1038\/s41586-022-05221-y","volume":"609","author":"NN Laqtom","year":"2022","unstructured":"Laqtom, N. N. et al. CLN3 is required for the clearance of glycerophosphodiesters from lysosomes. Nature 609, 1005\u20131011 (2022).","journal-title":"Nature"},{"key":"2059_CR37","doi-asserted-by":"publisher","first-page":"4651","DOI":"10.1016\/j.cell.2021.08.002","volume":"184","author":"T Logan","year":"2021","unstructured":"Logan, T. et al. Rescue of a lysosomal storage disorder caused by Grn loss of function with a brain penetrant progranulin biologic. Cell 184, 4651\u20134668 (2021).","journal-title":"Cell"},{"key":"2059_CR38","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-33500-9","volume":"13","author":"S Boland","year":"2022","unstructured":"Boland, S. et al. Deficiency of the frontotemporal dementia gene GRN results in gangliosidosis. Nat. Commun. 13, 5924 (2022).","journal-title":"Nat. Commun."},{"key":"2059_CR39","doi-asserted-by":"publisher","first-page":"1370","DOI":"10.1038\/s41556-018-0228-7","volume":"20","author":"A Di Ronza","year":"2018","unstructured":"Di Ronza, A. et al. CLN8 is an endoplasmic reticulum cargo receptor that regulates lysosome biogenesis. Nat. Cell Biol. 20, 1370\u20131377 (2018).","journal-title":"Nat. Cell Biol."},{"key":"2059_CR40","first-page":"4118","volume":"130","author":"L Bajaj","year":"2020","unstructured":"Bajaj, L. et al. A CLN6-CLN8 complex recruits lysosomal enzymes at the ER for Golgi transfer. J. Clin. Invest. 130, 4118\u20134132 (2020).","journal-title":"J. Clin. Invest."},{"key":"2059_CR41","doi-asserted-by":"publisher","unstructured":"Sheokand, et al. The Batten disease protein CLN8 is a stereospecific acyltransferase in bis(monoacylglycero)phosphate biosynthesis. Nat. Cell Biol. https:\/\/doi.org\/10.1038\/s41556-026-02061-0 (2026).","DOI":"10.1038\/s41556-026-02061-0"},{"key":"2059_CR42","doi-asserted-by":"publisher","first-page":"6834","DOI":"10.1016\/S0021-9258(20)89576-3","volume":"266","author":"T Thornburg","year":"1991","unstructured":"Thornburg, T., Miller, C., Thuren, T., King, L. & Waite, M. Glycerol reorientation during the conversion of phosphatidylglycerol to bis(monoacylglycerol)phosphate in macrophage-like RAW 264.7 cells. J. Biol. Chem. 266, 6834\u20136840 (1991).","journal-title":"J. Biol. Chem."},{"key":"2059_CR43","doi-asserted-by":"publisher","first-page":"1794","DOI":"10.1194\/jlr.M800129-JLR200","volume":"49","author":"K St\u00e5lberg","year":"2008","unstructured":"St\u00e5lberg, K., Neal, A. C., Ronne, H. & St\u00e5hl, U. Identification of a novel GPCAT activity and a new pathway for phosphatidylcholine biosynthesis in S. cerevisiae. J. Lipid Res. 49, 1794\u20131806 (2008).","journal-title":"J. Lipid Res."},{"key":"2059_CR44","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1007\/s00425-014-2184-1","volume":"241","author":"I Lager","year":"2015","unstructured":"Lager, I. et al. Novel reactions in acyl editing of phosphatidylcholine by lysophosphatidylcholine transacylase (LPCT) and acyl-CoA:glycerophosphocholine acyltransferase (GPCAT) activities in microsomal preparations of plant tissues. Planta 241, 347\u2013358 (2015).","journal-title":"Planta"},{"key":"2059_CR45","doi-asserted-by":"publisher","DOI":"10.1016\/j.jlr.2024.100685","volume":"65","author":"J Breithofer","year":"2024","unstructured":"Breithofer, J. et al. Phospholipase A2 group IVD mediates the transacylation of glycerophospholipids and acylglycerols. J. Lipid Res. 65, 100685 (2024).","journal-title":"J. Lipid Res."},{"key":"2059_CR46","doi-asserted-by":"publisher","first-page":"W171","DOI":"10.1093\/nar\/gkz365","volume":"47","author":"K Labun","year":"2019","unstructured":"Labun, K. et al. CHOPCHOP v3: expanding the CRISPR web toolbox beyond genome editing. Nucleic Acids Res. 47, W171\u2013W174 (2019).","journal-title":"Nucleic Acids Res."},{"key":"2059_CR47","doi-asserted-by":"publisher","first-page":"13488","DOI":"10.1074\/jbc.M314032200","volume":"279","author":"TM Lewin","year":"2004","unstructured":"Lewin, T. M., Schwerbrock, N. M. J., Lee, D. P. & Coleman, R. A. Identification of a new glycerol-3-phosphate acyltransferase isoenzyme, mtGPAT2, in mitochondria. J. Biol. Chem. 279, 13488\u201313495 (2004).","journal-title":"J. Biol. Chem."},{"key":"2059_CR48","doi-asserted-by":"publisher","first-page":"1137","DOI":"10.1194\/jlr.D700041-JLR200","volume":"49","author":"V Matyash","year":"2008","unstructured":"Matyash, V., Liebisch, G., Kurzchalia, T. V., Shevchenko, A. & Schwudke, D. Lipid extraction by methyl-tert-butyl ether for high-throughput lipidomics. J. Lipid Res. 49, 1137\u20131146 (2008).","journal-title":"J. Lipid Res."},{"key":"2059_CR49","doi-asserted-by":"publisher","first-page":"1909","DOI":"10.1038\/s44318-025-00439-8","volume":"45","author":"S Riedelbauch","year":"2026","unstructured":"Riedelbauch, S. et al. Recurrent innovation of protein-protein interactions in the Drosophila piRNA pathway. EMBO J. 45, 1909\u20131932 (2026).","journal-title":"EMBO J."},{"key":"2059_CR50","doi-asserted-by":"publisher","unstructured":"Dong, W. et al. Robust analytical methods for bis(monoacylglycero)phosphate profiling in health and disease. Nat. Protoc.https:\/\/doi.org\/10.1038\/s41596-026-01379-1 (2026).","DOI":"10.1038\/s41596-026-01379-1"}],"container-title":["Nature Cell Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41556-026-02059-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41556-026-02059-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41556-026-02059-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T23:16:01Z","timestamp":1791933361000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41556-026-02059-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,15]]},"references-count":50,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["2059"],"URL":"https:\/\/doi.org\/10.1038\/s41556-026-02059-8","relation":{},"ISSN":["1465-7392","1476-4679"],"issn-type":[{"value":"1465-7392","type":"print"},{"value":"1476-4679","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,15]]},"assertion":[{"value":"19 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 August 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 September 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}]}}