{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T01:05:21Z","timestamp":1783386321613,"version":"3.54.6"},"reference-count":93,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T00:00:00Z","timestamp":1756166400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH\/NEI","award":["EY019949"],"award-info":[{"award-number":["EY019949"]}]},{"name":"NIH\/NEI","award":["EY030970"],"award-info":[{"award-number":["EY030970"]}]},{"name":"NIH\/NEI","award":["EY035810"],"award-info":[{"award-number":["EY035810"]}]},{"name":"NIH\/NEI","award":["EY036132"],"award-info":[{"award-number":["EY036132"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Age-related macular degeneration (AMD) is a common eye disease that significantly affects daily activities and impedes the quality of life in aging adults, yet effective treatments to halt or reverse disease progression are currently lacking. Ongoing research aims at understanding the complex mechanisms underlying AMD pathophysiology involving retinal pigment epithelium (RPE) dysfunction, drusen formation, inflammation, neovascularization, and RPE\/photoreceptor degeneration. Sigma 2 receptor\/transmembrane protein 97 (\u03c32R\/TMEM97) is a multifunctional protein implicated in cellular processes including cholesterol homeostasis, lysosome-dependent autophagy, calcium homeostasis, and integrated stress response (ISR). Recent genome-wide association studies (GWASs) have identified \u03c32R\/TMEM97 as a novel genetic risk factor strongly associated with AMD development. In this review, we summarize recent research progress on \u03c32R\/TMEM97 in age-related neurodegenerative diseases, highlighting its implication as a molecular target in AMD via regulating oxidative stress, inflammation, lipid uptake, drusen formation, and epithelial\u2013mesenchymal transition (EMT). We also discuss the potential of modulating \u03c32R\/TMEM97 function with novel small-molecule drugs as a promising treatment for dry AMD and the unresolved questions in understanding the mechanistic basis of their actions.<\/jats:p>","DOI":"10.3390\/biom15091228","type":"journal-article","created":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T10:35:17Z","timestamp":1756204517000},"page":"1228","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Transmembrane Protein 97 (TMEM97): Molecular Target and Treatment in Age-Related Macular Degeneration (AMD)"],"prefix":"10.3390","volume":"15","author":[{"given":"Alyssa","family":"Stathopoulos","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Ira G. and Ross Eye Institute, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, 955 Main Street, Buffalo, NY 14203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua J.","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Ira G. and Ross Eye Institute, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, 955 Main Street, Buffalo, NY 14203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen F.","family":"Martin","sequence":"additional","affiliation":[{"name":"Department of Chemistry, The University of Texas at Austin, Austin, TX 78712, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah X.","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Ira G. and Ross Eye Institute, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, 955 Main Street, Buffalo, NY 14203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e339","DOI":"10.1016\/S2214-109X(13)70113-X","article-title":"Causes of vision loss worldwide, 1990\u20132010: A systematic analysis","volume":"1","author":"Bourne","year":"2013","journal-title":"Lancet Glob. 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