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The previous studies have demonstrated that induced retinal pigment epithelial (iRPE) cells generated by transcription factor\u2010mediated reprogramming exhibit superior therapeutic efficacy in treating AMD. In this study, it is found that these iRPE cells are resistant to ferroptosis and further identified phosphoethanolamine\/phosphocholine phosphatase 1 (PHOSPHO1) as a critical regulator underlying ferroptosis resistance. Mechanistically, PHOSPHO1 inhibits ferroptosis through two distinct mechanisms. First, it reduces PE levels in the endoplasmic reticulum, thereby limiting PE\u2010derived lipid peroxidation. Second, it suppresses autophagy and ferritinophagy, leading to a reduction in intracellular free iron accumulation. Experiments using an in vivo rat model confirm that PHOSPHO1 effectively protects RPE cells from ferroptotic damage. These findings highlight PHOSPHO1 as a potential therapeutic target for AMD, providing insights into novel ferroptosis\u2010based intervention strategies.<\/jats:p>","DOI":"10.1002\/advs.202505359","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T09:49:42Z","timestamp":1747820982000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["PHOSPHO1 Suppresses Ferroptosis in Retinal Pigment Epithelial Cells by Reducing the Levels of Phosphatidylethanolamine Molecular Species"],"prefix":"10.1002","volume":"12","author":[{"given":"Zhiyang","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Ophthalmology of Tongji Hospital and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute School of Medicine Tongji University  Shanghai 200065 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