{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:08:18Z","timestamp":1779149298186,"version":"3.51.4"},"reference-count":71,"publisher":"American Society for Clinical Investigation","issue":"15","license":[{"start":{"date-parts":[[2022,8,8]],"date-time":"2022-08-08T00:00:00Z","timestamp":1659916800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National Institute of Deafness and Other Communication Disorders","award":["R01DC019345"],"award-info":[{"award-number":["R01DC019345"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,8,8]]},"abstract":"<jats:p>\n                    Ciliopathies are a class of genetic diseases resulting in cilia dysfunction in multiple organ systems, including the olfactory system. Currently, there are no available curative treatments for olfactory dysfunction and other symptoms in ciliopathies. The loss or shortening of olfactory cilia, as seen in multiple mouse models of the ciliopathy Bardet\u2013Biedl syndrome (BBS), results in olfactory dysfunction. However, the underlying mechanism of the olfactory cilia reduction is unknown, thus limiting the development of therapeutic approaches for BBS and other ciliopathies. Here, we demonstrated that phosphatidylinositol 4,5-bisphosphate [PI(4,5)P\n                    <jats:sub>2<\/jats:sub>\n                    ], a phosphoinositide typically excluded from olfactory cilia, aberrantly redistributed into the residual cilia of BBS mouse models, which caused F-actin ciliary infiltration. Importantly, PI(4,5)P\n                    <jats:sub>2<\/jats:sub>\n                    and F-actin were necessary for olfactory cilia shortening. Using a gene therapeutic approach, the hydrolyzation of PI(4,5)P\n                    <jats:sub>2<\/jats:sub>\n                    by overexpression of inositol polyphosphate-5-phosphatase E (INPP5E) restored cilia length and rescued odor detection and odor perception in BBS. Together, our data indicate that PI(4,5)P\n                    <jats:sub>2<\/jats:sub>\n                    \/F-actin\u2013dependent cilia disassembly is a common mechanism contributing to the loss of olfactory cilia in BBS and provide valuable pan-therapeutic intervention targets for the treatment of ciliopathies.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.158736","type":"journal-article","created":{"date-parts":[[2022,7,8]],"date-time":"2022-07-08T09:29:56Z","timestamp":1657272596000},"source":"Crossref","is-referenced-by-count":4,"title":["Reversal of ciliary mechanisms of disassembly rescues olfactory dysfunction in ciliopathies"],"prefix":"10.1172","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7645-1922","authenticated-orcid":true,"given":"Chao","family":"Xie","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Therapeutics and"},{"name":"Center for Smell and Taste, University of Florida College of Medicine, Gainesville, 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