{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T23:15:34Z","timestamp":1792451734593,"version":"4.5.0"},"reference-count":57,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"6663","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Science"],"published-print":{"date-parts":[[2023,9,15]]},"abstract":"<jats:p>Lysosomes critically rely on bis(monoacylglycero)phosphate (BMP) to stimulate lipid catabolism, cholesterol homeostasis, and lysosomal function. Alterations in BMP levels in monogenic and complex neurodegeneration suggest an essential function in human health. However, the site and mechanism responsible for BMP synthesis have been subject to debate for decades. Here, we report that the Batten disease gene product CLN5 is the elusive BMP synthase (BMPS). BMPS-deficient cells exhibited a massive accumulation of the BMP synthesis precursor lysophosphatidylglycerol (LPG), depletion of BMP species, and dysfunctional lipid metabolism. Mechanistically, we found that BMPS mediated synthesis through an energy-independent base exchange reaction between two LPG molecules with increased activity on BMP-laden vesicles. Our study elucidates BMP biosynthesis and reveals an anabolic function of late endosomes\/lysosomes.<\/jats:p>","DOI":"10.1126\/science.adg9288","type":"journal-article","created":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T13:58:58Z","timestamp":1694699938000},"page":"1182-1189","update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":101,"title":["The Batten disease gene product CLN5 is the lysosomal bis(monoacylglycero)phosphate synthase"],"prefix":"10.1126","volume":"381","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7670-4093","authenticated-orcid":true,"given":"Uche N.","family":"Medoh","sequence":"first","affiliation":[{"name":"Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA."},{"name":"Department of Genetics, Stanford University, Stanford, CA 94305, USA."},{"name":"The Institute for Chemistry, Engineering &amp; Medicine for Human Health (Sarafan ChEM-H), Stanford University, Stanford, CA 94305, USA."},{"name":"Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4667-1892","authenticated-orcid":true,"given":"Andy","family":"Hims","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA."},{"name":"Department of Genetics, Stanford University, Stanford, CA 94305, USA."},{"name":"The Institute for Chemistry, Engineering &amp; Medicine for Human Health (Sarafan ChEM-H), Stanford University, Stanford, CA 94305, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7313-2501","authenticated-orcid":true,"given":"Julie Y.","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA."},{"name":"Department of Genetics, Stanford University, Stanford, CA 94305, USA."},{"name":"The Institute for Chemistry, Engineering &amp; Medicine for Human Health (Sarafan ChEM-H), Stanford University, Stanford, CA 94305, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5352-0072","authenticated-orcid":true,"given":"Ali","family":"Ghoochani","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA."},{"name":"Department of Genetics, Stanford University, Stanford, CA 94305, USA."},{"name":"The Institute for Chemistry, Engineering &amp; Medicine for Human Health (Sarafan ChEM-H), Stanford University, Stanford, CA 94305, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8898-4689","authenticated-orcid":true,"given":"Kwamina","family":"Nyame","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA."},{"name":"Department of Genetics, Stanford University, Stanford, CA 94305, USA."},{"name":"The Institute for Chemistry, Engineering &amp; Medicine for Human Health (Sarafan ChEM-H), Stanford University, Stanford, CA 94305, USA."},{"name":"Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5490-4265","authenticated-orcid":true,"given":"Wentao","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA."},{"name":"Department of Genetics, Stanford University, Stanford, CA 94305, USA."},{"name":"The Institute for Chemistry, Engineering &amp; Medicine for Human Health (Sarafan ChEM-H), Stanford University, Stanford, CA 94305, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3772-0477","authenticated-orcid":true,"given":"Monther","family":"Abu-Remaileh","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA."},{"name":"Department of Genetics, Stanford University, Stanford, CA 94305, USA."},{"name":"The Institute for Chemistry, Engineering &amp; Medicine for Human Health (Sarafan ChEM-H), Stanford University, Stanford, CA 94305, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0009-3084(67)90032-1"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/1462-2920.15777"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-010-0337-6"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1092425"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M900008-JLR200"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coisb.2021.100408"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-022-01881-6"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.27818"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.08.002"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-33500-9"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2013.03.017"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2014.06.014"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.700856"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2013.04.003"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2016.03.016"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature08710"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1042\/BST20170130"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2021.100813"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201847055"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abq7374"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21218067"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-021-03813-x"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-018-0025-4"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2015.05.011"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05221-y"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aan6298"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/32440"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M700154-JLR200"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)33243-X"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi961164o"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi961164o"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi961164o"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abj8633"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00438a031"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0074299"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1042\/BCJ20210171"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.06726-11"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2012.08.013"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.32.18711"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.46.30271"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1515\/BC.2001.035"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M202838200"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-nutr-071813-105541"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adf8966"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M801463200"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.50832"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/975"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-014-9748-x"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-023-04573-z"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(20)89576-3"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2021.12.004"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abm5578"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddy076"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI130955"},{"key":"e_1_3_2_56_2","unstructured":"U. N. Medoh Lipidomic analysis of WT and CLN5-deficient HEK293T cells iPSCs and iNeurons. Dryad (2023); https:\/\/datadryad.org\/stash\/dataset\/doi:10.5061\/dryad.gb5mkkwvq."},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aao3265"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1002\/cpcb.51"}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.adg9288","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,15]],"date-time":"2024-01-15T19:33:39Z","timestamp":1705347219000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.adg9288"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,15]]},"references-count":57,"journal-issue":{"issue":"6663","published-print":{"date-parts":[[2023,9,15]]}},"alternative-id":["10.1126\/science.adg9288"],"URL":"https:\/\/doi.org\/10.1126\/science.adg9288","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.742779366.793600859","asserted-by":"object"}]},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,15]]},"assertion":[{"value":"2023-01-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-08-16","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-09-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}