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Yet, the mechanism of autophagy in the RPE remains largely unknown. RP is an inherited retinal degenerative condition, whose candidate genes provide avenues for dissecting novel autophagy factors. Here, whole exome sequencing of RP patients identified biallelic variants in\n                    <jats:italic>TRIM49<\/jats:italic>\n                    , a primate\u2010specific gene involved in autophagy, as a novel cause of RP. Among human tissues TRIM49 is highly expressed in the RPE. In human RPE cells, deficiency of\n                    <jats:italic>TRIM49<\/jats:italic>\n                    significantly disturbs cellular homeostasis and impairs the POS phagocytosis. Importantly, suppressed basal autophagy flux is present in\n                    <jats:italic>TRIM49<\/jats:italic>\n                    \u2010depleted RPE cells, whereas enhanced autophagy flux is present in RPE cells overexpressing\n                    <jats:italic>TRIM49<\/jats:italic>\n                    . Variations of TRIM49 after treatment with multiple autophagy modulators indicate that\n                    <jats:italic>TRIM49<\/jats:italic>\n                    is involved in the initiation of autophagy. TRIM49 interacts with the key regulator of autophagy initiation ULK1. Deficiency of\n                    <jats:italic>TRIM49<\/jats:italic>\n                    down\u2010regulates and overexpression of\n                    <jats:italic>TRIM49<\/jats:italic>\n                    up\u2010regulates ULK1 expression. Altogether, these findings identify\n                    <jats:italic>TRIM49<\/jats:italic>\n                    as a critical regulator of ULK1\u2010mediated autophagy and POS phagocytosis by the RPE, suggesting that RPE autophagy is a potential therapeutic target for retinal degenerative diseases.\n                  <\/jats:p>","DOI":"10.1002\/advs.202512305","type":"journal-article","created":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T14:52:40Z","timestamp":1758034360000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Retinitis Pigmentosa\u2010Associated Gene\n                    <i>TRIM49<\/i>\n                    Regulates ULK1\u2010Mediated Autophagy and Photoreceptor Phagocytosis by the Retinal Pigment Epithelium"],"prefix":"10.1002","volume":"12","author":[{"given":"Zhen","family":"Yi","sequence":"first","affiliation":[{"name":"State Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center 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