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The neural retina exhibits one of the highest energetic and redox demands in the body, yet mechanisms governing local flavin homeostasis remain poorly defined. Retbindin (RTBDN), a retina\u2010specific riboflavin\u2010binding protein, has previously been shown to regulate total retinal flavin levels and photoreceptor survival. Here, we demonstrate that RTBDN abundance and subcellular localization are dynamically modulated by developmental stage, riboflavin availability, and the light\u2013dark cycle. RTBDN expression emerges during outer segment maturation, peaks in early adulthood, and declines with aging in parallel with retinal flavin content. Fasting reduces retinal flavin levels without altering total RTBDN protein abundance but induces redistribution of RTBDN from the outer segment\u2010RPE interface toward cone\u2010associated domains. Riboflavin repletion restores its localization. Similarly, RTBDN redistributes around cones during the dark phase and returns to outer segment tips at light onset, independent of changes in total protein levels. These findings identify RTBDN as a spatially dynamic regulator of flavin\u2010dependent homeostasis that adapts to nutrient flux and circadian metabolic demand. This adaptive redistribution may represent a protective mechanism to preserve cone function under fluctuating energetic conditions and suggests that disruption of flavin homeostasis may contribute to cone degeneration.<\/jats:p>","DOI":"10.1096\/fj.202601497rr","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T15:32:07Z","timestamp":1790004727000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Retbindin Dynamically Redistributes to Preserve Retinal Flavin\u2010Dependent Homeostasis in Response to Riboflavin Availability and Circadian Demand"],"prefix":"10.1096","volume":"40","author":[{"given":"Xue","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering University of Houston  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustafa S.","family":"Makia","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Houston  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0909-2469","authenticated-orcid":false,"given":"Gennadiy P.","family":"Moiseyev","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Wake Forest University School of Medicine  Winston\u2010Salem North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muna I.","family":"Naash","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Houston  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4914-350X","authenticated-orcid":false,"given":"Muayyad R.","family":"Al\u2010Ubaidi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Houston  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/77.6.1352"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2006.04.014"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpa.2007.01.010"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.2174\/1381612811319140014"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2015.08.013"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/10408398.2016.1145104"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21030950"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.00861"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nutres.2023.08.010"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.afnr.2017.11.002"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12058"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2021.108023"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-nutr-061121-084407"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.2105\/AJPH.31.4.344"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(75)90799-8"},{"key":"e_1_2_11_17_1","first-page":"182","article-title":"Riboflavin Metabolism\u2014Relevance to Human Nutrition","volume":"108","author":"Lakshmi A. 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