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We used super-resolution fluorescence microscopy and electron microscopy to localize CEP290 in the CC and in the primary cilia of cultured cells with subdiffraction resolution and to determine effects of CEP290 deficiency in 3 mutant models. Radially, CEP290 localizes in close proximity to the microtubule doublets in the region between the doublets and the ciliary membrane. Longitudinally, it is distributed throughout the length of the CC whereas it is confined to the very base of primary cilia in human retinal pigment epithelium-1 cells. We found Y-shaped links, ciliary substructures between microtubules and membrane, throughout the length of the CC. Severe CEP290 deficiencies in mouse models did not prevent assembly of cilia or cause obvious mislocalization of ciliary components in early stages of degeneration. There were fewer cilia and no normal outer segments in the mutants, but the Y-shaped links were clearly present. These results point to photoreceptor-specific functions of CEP290 essential for CC maturation and stability following the earliest stages of ciliogenesis.<\/jats:p>","DOI":"10.1172\/jci.insight.145256","type":"journal-article","created":{"date-parts":[[2021,9,14]],"date-time":"2021-09-14T12:00:37Z","timestamp":1631620837000},"source":"Crossref","is-referenced-by-count":30,"title":["Super-resolution microscopy reveals photoreceptor-specific subciliary location and function of ciliopathy-associated protein CEP290"],"prefix":"10.1172","volume":"6","author":[{"given":"Valencia L.","family":"Potter","sequence":"first","affiliation":[{"name":"Verna and Marrs McLean Department of Biochemistry and Molecular Biology,"},{"name":"Program in Developmental Biology, Graduate School of Biomedical Sciences, and"},{"name":"Medical Scientist Training Program, Baylor College of Medicine, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail 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