{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T05:51:14Z","timestamp":1792648274771,"version":"4.5.0"},"reference-count":37,"publisher":"National Academy of Sciences","issue":"41","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2014,10,14]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>Many rare human genetic disorders are caused by mutations in genes that code for proteins of poorly characterized function. Determining the functions of these proteins is critical for understanding and devising potential treatments for human diseases. In this article, we discover using a combination of mouse genetic models, selective inhibitors, and lipid profiling that the DDHD2 enzyme, mutations of which cause a neurological disease termed complex hereditary spastic paraplegia (HSP), acts as a major brain triglyceride hydrolase. Mice lacking DDHD2 have elevated brain triglycerides and lipid droplet accumulation in neurons. We have thus discovered that the brain possesses a specialized pathway for triglyceride metabolism, disruption of which leads to biochemical and cellular changes that may contribute to complex HSP.<\/jats:p>","DOI":"10.1073\/pnas.1413706111","type":"journal-article","created":{"date-parts":[[2014,9,30]],"date-time":"2014-09-30T11:28:38Z","timestamp":1412076518000},"page":"14924-14929","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":178,"title":["The hereditary spastic paraplegia-related enzyme DDHD2 is a principal brain triglyceride lipase"],"prefix":"10.1073","volume":"111","author":[{"given":"Jordon M.","family":"Inloes","sequence":"first","affiliation":[{"name":"The Skaggs Institute for Chemical Biology and"},{"name":"Departments of bChemical Physiology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5620-3972","authenticated-orcid":false,"given":"Ku-Lung","family":"Hsu","sequence":"additional","affiliation":[{"name":"The Skaggs Institute for Chemical Biology and"},{"name":"Departments of bChemical Physiology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa M.","family":"Dix","sequence":"additional","affiliation":[{"name":"The Skaggs Institute for Chemical Biology and"},{"name":"Departments of bChemical Physiology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreu","family":"Viader","sequence":"additional","affiliation":[{"name":"The Skaggs Institute for Chemical Biology and"},{"name":"Departments of bChemical Physiology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"Masuda","sequence":"additional","affiliation":[{"name":"The Skaggs Institute for Chemical Biology and"},{"name":"Departments of bChemical Physiology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thais","family":"Takei","sequence":"additional","affiliation":[{"name":"The Skaggs Institute for Chemical Biology and"},{"name":"Departments of bChemical Physiology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malcolm R.","family":"Wood","sequence":"additional","affiliation":[{"name":"Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin F.","family":"Cravatt","sequence":"additional","affiliation":[{"name":"The Skaggs Institute for Chemical Biology and"},{"name":"Departments of bChemical Physiology and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2014,9,29]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2012.91"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-013-1115-8"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1247363"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2007.12.018"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.11.001"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.10.017"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2013.29"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-013-7206-6"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111092200"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.10.5468"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M200330200"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2011.01.014"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi0480335"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R109.097600"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2013.03.031"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/85686"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm400898x"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1037\/h0077579"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1021\/ac051437y"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1044-0305(99)00035-5"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2007.03.012"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1123965"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-408051-5.00012-7"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2012.02.002"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1100747"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2008.10.005"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1951"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00099.2009"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2011.07498.x"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.29.20505"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M600161-JLR200"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-014-7418-4"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.1359"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R800018-JLR200"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M013003"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201402069"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1217121110"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1413706111","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T23:38:21Z","timestamp":1649806701000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1413706111"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,9,29]]},"references-count":37,"journal-issue":{"issue":"41","published-print":{"date-parts":[[2014,10,14]]}},"alternative-id":["10.1073\/pnas.1413706111"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1413706111","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,9,29]]},"assertion":[{"value":"2014-09-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}