{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T20:57:55Z","timestamp":1782853075617,"version":"3.54.5"},"reference-count":79,"publisher":"American Society for Cell Biology (ASCB)","issue":"21","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MBoC"],"published-print":{"date-parts":[[2013,11]]},"abstract":"<jats:p>Niemann\u2013Pick disease type C (NPC) is caused by mutations in NPC1 or NPC2, which coordinate egress of low-density-lipoprotein (LDL)-cholesterol from late endosomes. We previously reported that the adenovirus-encoded protein RID\u03b1 rescues the cholesterol storage phenotype in NPC1-mutant fibroblasts. We show here that RID\u03b1 reconstitutes deficient endosome-to-endoplasmic reticulum (ER) transport, allowing excess LDL-cholesterol to be esterified by acyl-CoA:cholesterol acyltransferase and stored in lipid droplets (LDs) in NPC1-deficient cells. Furthermore, the RID\u03b1 pathway is regulated by the oxysterol-binding protein ORP1L. Studies have classified ORP1L as a sterol sensor involved in LE positioning downstream of GTP-Rab7. Our data, however, suggest that ORP1L may play a role in transport of LDL-cholesterol to a specific ER pool designated for LD formation. In contrast to NPC1, which is dispensable, the RID\u03b1\/ORP1L-dependent route requires functional NPC2. Although NPC1\/NPC2 constitutes the major pathway, therapies that amplify minor egress routes for LDL-cholesterol could significantly improve clinical management of patients with loss-of-function NPC1 mutations. The molecular identity of putative alternative pathways, however, is poorly characterized. We propose RID\u03b1 as a model system for understanding physiological egress routes that use ORP1L to activate ER feedback responses involved in LD formation.<\/jats:p>","DOI":"10.1091\/mbc.e12-10-0760","type":"journal-article","created":{"date-parts":[[2013,9,12]],"date-time":"2013-09-12T02:09:48Z","timestamp":1378951788000},"page":"3309-3325","source":"Crossref","is-referenced-by-count":39,"title":["Adenovirus RID\u03b1 uncovers a novel pathway requiring ORP1L for lipid droplet formation independent of NPC1"],"prefix":"10.1091","volume":"24","author":[{"given":"Nicholas L.","family":"Cianciola","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and Microbiology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane J.","family":"Greene","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Lerner Research Institute, Cleveland Clinic Foundation, 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