Luo, NaWest, Callah C.Murga-Zamalloa, Carlos A.Sun, LouAnderson, Ryan M.Wells, Clark D.Weinreb, Robert N.Travers, Jeffrey B.Khanna, HemantSun, Yang2025-07-072025-07-072012Luo N, West CC, Murga-Zamalloa CA, et al. OCRL localizes to the primary cilium: a new role for cilia in Lowe syndrome. Hum Mol Genet. 2012;21(15):3333-3344. doi:10.1093/hmg/dds163https://hdl.handle.net/1805/49188Oculocerebral renal syndrome of Lowe (OCRL or Lowe syndrome), a severe X-linked congenital disorder characterized by congenital cataracts and glaucoma, mental retardation and kidney dysfunction, is caused by mutations in the OCRL gene. OCRL is a phosphoinositide 5-phosphatase that interacts with small GTPases and is involved in intracellular trafficking. Despite extensive studies, it is unclear how OCRL mutations result in a myriad of phenotypes found in Lowe syndrome. Our results show that OCRL localizes to the primary cilium of retinal pigment epithelial cells, fibroblasts and kidney tubular cells. Lowe syndrome-associated mutations in OCRL result in shortened cilia and this phenotype can be rescued by the introduction of wild-type OCRL; in vivo, knockdown of ocrl in zebrafish embryos results in defective cilia formation in Kupffer vesicles and cilia-dependent phenotypes. Cumulatively, our data provide evidence for a role of OCRL in cilia maintenance and suggest the involvement of ciliary dysfunction in the manifestation of Lowe syndrome.en-USAttribution-NonCommercial 4.0 InternationalCiliaKidney tubulesPhosphoric monoester hydrolasesOculocerebrorenal syndromeImmunohistochemistryArticle