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However, the molecular mechanisms underlying the photoreceptor cilium integrity and retinal homeostasis are largely unknown. Herein, it is shown that kinesin family member 11 (KIF11) localizes at the transition zone (connecting cilium) of the photoreceptor and plays a crucial role in orchestrating the cilium integrity. KIF11 depletion causes malformations of both the photoreceptor ciliary axoneme and membranous discs, resulting in photoreceptor degeneration and the accumulation of drusen\u2010like deposits throughout the retina. Mechanistic studies show that the stability of KIF11 is regulated by an interplay between its UFMylation and ubiquitination; UFMylation of KIF11 at lysine 953 inhibits its ubiquitination by synoviolin 1 and thereby prevents its proteasomal degradation. The lysine 953\u2010to\u2010arginine mutant of KIF11 is more stable than wild\u2010type KIF11 and also more effective in reversing the ciliary and retinal defects induced by KIF11 depletion. These findings identify a critical role for KIF11 UFMylation in the maintenance of photoreceptor cilium integrity and retinal homeostasis.<\/jats:p>","DOI":"10.1002\/advs.202400569","type":"journal-article","created":{"date-parts":[[2024,4,26]],"date-time":"2024-04-26T05:00:20Z","timestamp":1714107620000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["KIF11 UFMylation Maintains Photoreceptor Cilium Integrity and Retinal Homeostasis"],"prefix":"10.1002","volume":"11","author":[{"given":"Jie","family":"Ran","sequence":"first","affiliation":[{"name":"Center for Cell Structure and Function Shandong Provincial Key Laboratory of Animal Resistance Biology Haihe Laboratory of Cell Ecosystem College of Life Sciences Shandong Normal University  Jinan 250014 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guizhi","family":"Guo","sequence":"additional","affiliation":[{"name":"Center for Cell Structure 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