{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T07:56:43Z","timestamp":1793692603282,"version":"4.5.1"},"reference-count":53,"publisher":"National Academy of Sciences","issue":"48","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2012,11,27]]},"abstract":"<jats:p>Mutations affecting ciliary components cause a series of related genetic disorders in humans, including nephronophthisis (NPHP), Joubert syndrome (JBTS), Meckel-Gruber syndrome (MKS), and Bardet-Biedl syndrome (BBS), which are collectively termed \u201cciliopathies.\u201d Recent protein\u2013protein interaction studies combined with genetic analyses revealed that ciliopathy-related proteins form several functional networks\/modules that build and maintain the primary cilium. However, the precise function of many ciliopathy-related proteins and the mechanisms by which these proteins are targeted to primary cilia are still not well understood. Here, we describe a protein\u2013protein interaction network of inositol polyphosphate-5-phosphatase E (INPP5E), a prenylated protein associated with JBTS, and its ciliary targeting mechanisms. INPP5E is targeted to the primary cilium through a motif near the C terminus and prenyl-binding protein phosphodiesterase 6D (PDE6D)-dependent mechanisms. Ciliary targeting of INPP5E is facilitated by another JBTS protein, ADP-ribosylation factor-like 13B (ARL13B), but not by ARL2 or ARL3. ARL13B missense mutations that cause JBTS in humans disrupt the ARL13B\u2013INPP5E interaction. We further demonstrate interactions of INPP5E with several ciliary and centrosomal proteins, including a recently identified ciliopathy protein centrosomal protein 164 (CEP164). These findings indicate that ARL13B, INPP5E, PDE6D, and CEP164 form a distinct functional network that is involved in JBTS and NPHP but independent of the ones previously defined by NPHP and MKS proteins.<\/jats:p>","DOI":"10.1073\/pnas.1210916109","type":"journal-article","created":{"date-parts":[[2012,11,13]],"date-time":"2012-11-13T13:32:23Z","timestamp":1352813543000},"page":"19691-19696","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":246,"title":["ARL13B, PDE6D, and CEP164 form a functional network for INPP5E ciliary targeting"],"prefix":"10.1073","volume":"109","author":[{"given":"Melissa C.","family":"Humbert","sequence":"first","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences,"},{"name":"Department of Pediatrics,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie","family":"Weihbrecht","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual 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and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seongjin","family":"Seo","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual 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