{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:19:37Z","timestamp":1785406777724,"version":"3.56.0"},"reference-count":75,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001694","name":"International Retinal Research Foundation","doi-asserted-by":"publisher","award":["GF02527"],"award-info":[{"award-number":["GF02527"]}],"id":[{"id":"10.13039\/100001694","id-type":"DOI","asserted-by":"publisher"}]},{"award":["GF02527"],"award-info":[{"award-number":["GF02527"]}],"id":[{"id":"https:\/\/ror.org\/04xsz1294","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001818","name":"Research to Prevent Blindness (RPB), Inc.","doi-asserted-by":"publisher","award":["R24EY028758"],"award-info":[{"award-number":["R24EY028758"]}],"id":[{"id":"10.13039\/100001818","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001818","name":"Research to Prevent Blindness (RPB), Inc.","doi-asserted-by":"publisher","award":["R24EY027285"],"award-info":[{"award-number":["R24EY027285"]}],"id":[{"id":"10.13039\/100001818","id-type":"DOI","asserted-by":"publisher"}]},{"award":["R24EY028758"],"award-info":[{"award-number":["R24EY028758"]}],"id":[{"id":"https:\/\/ror.org\/04drjs621","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R24EY027285"],"award-info":[{"award-number":["R24EY027285"]}],"id":[{"id":"https:\/\/ror.org\/04drjs621","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010657","name":"Carl Marshall and Mildred Reeves Foundation Macular Degeneration Research award","doi-asserted-by":"publisher","award":["GR020592"],"award-info":[{"award-number":["GR020592"]}],"id":[{"id":"10.13039\/100010657","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Margy Ann and J Donald M. Gass Chair endowment"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Prominin-1 (Prom1\/CD133) has long been recognized as a structural determinant of photoreceptor outer segment (OS) morphogenesis, yet rapidly accumulating evidence extends its role to retinal pigment epithelium (RPE) homeostasis, encompassing autophagy\u2013lysosomal flux, outer segment phagocytosis, mitochondrial function, and regulation of inflammatory stress. This review synthesizes mechanistic and transcriptomic insights that position PROM1 as a central regulator of photoreceptor and RPE integrity, reframing Prom1 disease as a multi-compartment retinal disorder relevant to both inherited retinal dystrophies (IRDs) and atrophic age-related macular degeneration (aAMD). We develop a dual-axis conceptual model in which Prom1 dysfunction can initiate pathology in either the photoreceptors (OS morphogenesis failure) or the RPE, including impaired autophagic flux, lysosomal activity, defective phagocytosis, and Epithelial-Mesenchymal Transition (EMT)-like de-differentiation, with secondary cross-compartmental degeneration. Clinically, autosomal-dominant missense variants associate with macular or cone-rod dystrophy, whereas biallelic truncating\/splice-site mutations drive early-onset rod\u2013cone disease and panretinal\/RPE atrophy, illustrating genotype\u2013phenotype diversity. By integrating recent high-resolution transcriptomic data from Prom1-deficient RPE cells with long-standing insights into photoreceptor biology, we highlight converging pathways of degeneration that challenge a photoreceptor-centric view and unify disparate phenotypes within a single molecular framework. These insights broaden the therapeutic landscape, advancing gene augmentation and pathway-targeted strategies to preserve RPE integrity, sustain photoreceptor function, and modify disease course in PROM1-associated IRDs and atrophic AMD.<\/jats:p>","DOI":"10.3390\/biom16050635","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T17:26:18Z","timestamp":1777051578000},"page":"635","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Prominin-1 and Retinal Degenerative Disorders: Expanding the Biology from Photoreceptors to the Retinal Pigment Epithelium"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4443-9691","authenticated-orcid":false,"given":"Sujoy","family":"Bhattacharya","sequence":"first","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5883-7212","authenticated-orcid":false,"given":"Caitlin","family":"Ang","sequence":"additional","affiliation":[{"name":"Barnard College of Columbia University, New York, NY 10027, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Soucy","sequence":"additional","affiliation":[{"name":"Departments of Pathology, Cell Biology, and Ophthalmology, Irving Medical Center, Columbia University, New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9082-2427","authenticated-orcid":false,"given":"Stephen H.","family":"Tsang","sequence":"additional","affiliation":[{"name":"Departments of Pathology, Cell Biology, and Ophthalmology, Irving Medical Center, Columbia University, New York, NY 10032, USA"},{"name":"Department of Biomedical Engineering, Columbia University, New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Chaum","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Rosa, J.G.S., Disner, G.R., Pinto, F.J., Lima, C., and Lopes-Ferreira, M. (2023). Revisiting Retinal Degeneration Hallmarks: Insights from Molecular Markers and Therapy Perspectives. Int. J. Mol. Sci., 24.","DOI":"10.20944\/preprints202307.0542.v1"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e1175","DOI":"10.1016\/S2214-109X(25)00143-3","article-title":"Global burden of vision impairment due to age-related macular degeneration, 1990-2021, with forecasts to 2050: A systematic analysis for the Global Burden of Disease Study 2021","volume":"13","author":"Collaborators","year":"2025","journal-title":"Lancet Glob. Health"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Manley, A., Meshkat, B.I., Jablonski, M.M., and Hollingsworth, T.J. (2023). Cellular and Molecular Mechanisms of Pathogenesis Underlying Inherited Retinal Dystrophies. Biomolecules, 13.","DOI":"10.3390\/biom13020271"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1111\/ceo.13917","article-title":"Inherited retinal diseases: Therapeutics, clinical trials and end points-A review","volume":"49","author":"Georgiou","year":"2021","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.preteyeres.2017.01.005","article-title":"Bestrophinopathy: An RPE-photoreceptor interface disease","volume":"58","author":"Guziewicz","year":"2017","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Cehajic Kapetanovic, J., Barnard, A.R., and MacLaren, R.E. (2019). Molecular Therapies for Choroideremia. Genes, 10.","DOI":"10.3390\/genes10100738"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/j.preteyeres.2010.04.002","article-title":"Leber congenital amaurosis due to RPE65 mutations and its treatment with gene therapy","volume":"29","author":"Cideciyan","year":"2010","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1167\/tvst.7.4.6","article-title":"Inherited Retinal Degenerations: Current Landscape and Knowledge Gaps","volume":"7","author":"Duncan","year":"2018","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.preteyeres.2017.03.002","article-title":"The impact of oxidative stress and inflammation on RPE degeneration in non-neovascular AMD","volume":"60","author":"Datta","year":"2017","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"100846","DOI":"10.1016\/j.preteyeres.2020.100846","article-title":"The cell biology of the retinal pigment epithelium","volume":"78","author":"Lakkaraju","year":"2020","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.trsl.2012.12.007","article-title":"Gene therapy for retinal disease","volume":"161","author":"McClements","year":"2013","journal-title":"Transl. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1093\/hmg\/9.1.27","article-title":"A frameshift mutation in prominin (mouse)-like 1 causes human retinal degeneration","volume":"9","author":"Maw","year":"2000","journal-title":"Hum. Mol. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1034\/j.1600-0854.2001.020202.x","article-title":"Prominin: A story of cholesterol, plasma membrane protrusions and human pathology","volume":"2","author":"Corbeil","year":"2001","journal-title":"Traffic"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1111\/tra.12618","article-title":"Prominin-1 (CD133) modulates the architecture and dynamics of microvilli","volume":"20","author":"Thamm","year":"2019","journal-title":"Traffic"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1038\/s41419-024-07105-7","article-title":"Deciphering the impact of PROM1 alternative splicing on human photoreceptor development and maturation","volume":"15","author":"Dorgau","year":"2024","journal-title":"Cell Death Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.ajo.2019.05.014","article-title":"Expanded Phenotypic Spectrum of Retinopathies Associated with Autosomal Recessive and Dominant Mutations in PROM1","volume":"207","author":"Arteche","year":"2019","journal-title":"Am. J. Ophthalmol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1002\/cne.901900307","article-title":"Disc morphogenesis in vertebrate photoreceptors","volume":"190","author":"Steinberg","year":"1980","journal-title":"J. Comp. Neurol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2297","DOI":"10.1523\/JNEUROSCI.2034-08.2009","article-title":"Loss of the cholesterol-binding protein prominin-1\/CD133 causes disk dysmorphogenesis and photoreceptor degeneration","volume":"29","author":"Zacchigna","year":"2009","journal-title":"J. Neurosci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.18240\/ijo.2021.09.07","article-title":"Deletion of prominin-1 in mice results in disrupted photoreceptor outer segment protein homeostasis","volume":"14","author":"Xiao","year":"2021","journal-title":"Int. J. Ophthalmol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"10498","DOI":"10.1038\/s41598-024-60989-5","article-title":"Prominin 1 is crucial for the early development of photoreceptor outer segments","volume":"14","author":"Yanardag","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_21","first-page":"2908","article-title":"Mutant prominin 1 found in patients with macular degeneration disrupts photoreceptor disk morphogenesis in mice","volume":"118","author":"Yang","year":"2008","journal-title":"J. Clin. Investig."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1007\/978-3-030-27378-1_79","article-title":"Prominin-1 and Photoreceptor Cadherin Localization in Xenopus laevis: Protein-Protein Relationships and Function","volume":"1185","author":"Carr","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1167\/iovs.14-15479","article-title":"Genetic background and light-dependent progression of photoreceptor cell degeneration in Prominin-1 knockout mice","volume":"56","author":"Dellett","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.ajo.2023.11.010","article-title":"Progression of PROM1-Associated Retinal Degeneration as Determined by Spectral-Domain Optical Coherence Tomography Over a 24-Month Period","volume":"259","author":"Grosspotzl","year":"2024","journal-title":"Am. J. Ophthalmol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Kong, M.D., Golebka, J., Anderson, V.R., Bao, C., Bailey, J.A., Exinor, A., Demirkol, A., and Tsang, S.H. (2025). Divergent Manifestations in Biallelic Versus Monoallelic Variants of RP1-, BEST1-, and PROM1-Associated Retinal Disorders. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26146615"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"21877","DOI":"10.1038\/s41598-023-49131-z","article-title":"Genetic and clinical characteristics of PROM1-related retinal degeneration in Korean","volume":"13","author":"Hwang","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"122","DOI":"10.18632\/oncotarget.22343","article-title":"Genetic identification and molecular modeling characterization reveal a novel PROM1 mutation in Stargardt4-like macular dystrophy","volume":"9","author":"Imani","year":"2018","journal-title":"Oncotarget"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4771","DOI":"10.1167\/iovs.09-4561","article-title":"The PROM1 mutation p.R373C causes an autosomal dominant bull\u2019s eye maculopathy associated with rod, rod-cone, and macular dystrophy","volume":"51","author":"Michaelides","year":"2010","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1007\/s00439-007-0395-2","article-title":"Severe retinitis pigmentosa mapped to 4p15 and associated with a novel mutation in the PROM1 gene","volume":"122","author":"Zhang","year":"2007","journal-title":"Hum. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1186\/s13287-024-03804-2","article-title":"Clinical exome analysis and targeted gene repair of the c.1354dupT variant in iPSC lines from patients with PROM1-related retinopathies exhibiting diverse phenotypes","volume":"15","author":"Gobelli","year":"2024","journal-title":"Stem Cell Res. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e195752","DOI":"10.1001\/jamanetworkopen.2019.5752","article-title":"Clinical and Molecular Characterization of PROM1-Related Retinal Degeneration","volume":"2","author":"Birtel","year":"2019","journal-title":"JAMA Netw. Open"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2373","DOI":"10.1002\/jcp.31094","article-title":"Loss of Prom1 impairs autophagy and promotes epithelial-mesenchymal transition in mouse retinal pigment epithelial cells","volume":"238","author":"Bhattacharya","year":"2023","journal-title":"J. Cell Physiol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Bhattacharya, S., Yang, T.S., Nabit, B.P., Krystofiak, E.S., Rex, T.S., and Chaum, E. (2024). Prominin-1 Knockdown Causes RPE Degeneration in a Mouse Model. Cells, 13.","DOI":"10.20944\/preprints202410.0669.v1"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2366","DOI":"10.1167\/iovs.16-21162","article-title":"Prominin-1 Is a Novel Regulator of Autophagy in the Human Retinal Pigment Epithelium","volume":"58","author":"Bhattacharya","year":"2017","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Huo, W., Yin, J., Ghose, P., Schafer, J.C., Chaum, E., and Bhattacharya, S. (2025). Prominin-1 Regulates Retinal Pigment Epithelium Homeostasis: Transcriptomic Insights into Degenerative Mechanisms. Int. J. Mol. Sci., 26.","DOI":"10.20944\/preprints202511.0189.v1"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"D\u2019Esposito, F., Gagliano, C., Vallone, S., Cappellani, F., Gagliano, G., Randazzo, V., Tognetto, D., Esposito, G., and Zeppieri, M. (2025). Clinical and Molecular Findings in PROM1-Associated Inherited Retinal Dystrophies. Genes, 16.","DOI":"10.3390\/genes16111299"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"422","DOI":"10.3928\/23258160-20220723-01","article-title":"Clinical Characterization of Autosomal Dominant and Autosomal Recessive PROM1 Mutation with a Report of Novel Mutation","volume":"53","author":"Lee","year":"2022","journal-title":"Ophthalmic Surg. Lasers Imaging Retin."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"pgad043","DOI":"10.1093\/pnasnexus\/pgad043","article-title":"The first genetic landscape of inherited retinal dystrophies in Portuguese patients identifies recurrent homozygous mutations as a frequent cause of pathogenesis","volume":"2","author":"Peter","year":"2023","journal-title":"PNAS Nexus"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1097\/IAE.0000000000003784","article-title":"Macular Atrophy and Phenotypic Variability in Autosomal Dominant Stargardt-Like Macular Dystrophy Due to Prom1 Mutation","volume":"43","author":"Ricca","year":"2023","journal-title":"Retina"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"101308","DOI":"10.1016\/j.preteyeres.2024.101308","article-title":"Dual inheritance patterns: A spectrum of non-syndromic inherited retinal disease phenotypes with varying molecular mechanisms","volume":"104","author":"Holtes","year":"2025","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"110453","DOI":"10.1016\/j.exer.2025.110453","article-title":"The pathogenicity of a novel frame-shift variant c.2321delC of PROM1 in an autosomal recessive cone-rod dystrophy pedigree may be associated with augment of autophagy","volume":"257","author":"Wu","year":"2025","journal-title":"Exp Eye Res"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.ajhg.2016.12.003","article-title":"Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease","volume":"100","author":"Carss","year":"2017","journal-title":"Am. J. Hum. Genet."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"536","DOI":"10.3343\/alm.2017.37.6.536","article-title":"Identification of the PROM1 Mutation p.R373C in a Korean Patient With Autosomal Dominant Stargardt-like Macular Dystrophy","volume":"37","author":"Kim","year":"2017","journal-title":"Ann. Lab. Med."},{"key":"ref_44","first-page":"1295","article-title":"An intronic deletion in the PROM1 gene leads to autosomal recessive cone-rod dystrophy","volume":"21","author":"Eidinger","year":"2015","journal-title":"Mol. Vis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1080\/13816810.2019.1660382","article-title":"Modification of the PROM1 disease phenotype by a mutation in ABCA4","volume":"40","author":"Lee","year":"2019","journal-title":"Ophthalmic Genet."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"a004481","DOI":"10.1101\/mcs.a004481","article-title":"Compound heterozygous novel frameshift variants in the PROM1 gene result in Leber congenital amaurosis","volume":"5","author":"Ragi","year":"2019","journal-title":"Cold Spring Harb. Mol. Case Stud."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2656","DOI":"10.1167\/iovs.09-4857","article-title":"Autosomal recessive retinitis pigmentosa with early macular affectation caused by premature truncation in PROM1","volume":"51","author":"Permanyer","year":"2010","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1080\/13816810.2016.1275022","article-title":"PROM1 gene variations in Brazilian patients with macular dystrophy","volume":"38","author":"Salles","year":"2017","journal-title":"Ophthalmic Genet."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1002\/ajmg.c.31826","article-title":"Clinical and genetic characteristics of 10 Japanese patients with PROM1-associated retinal disorder: A report of the phenotype spectrum and a literature review in the Japanese population","volume":"184","author":"Fujinami","year":"2020","journal-title":"Am. J. Med. Genet. C Semin. Med. Genet."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1186\/s13023-015-0300-3","article-title":"Next-generation sequencing applied to a large French cone and cone-rod dystrophy cohort: Mutation spectrum and new genotype-phenotype correlation","volume":"10","author":"Demontant","year":"2015","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"12425","DOI":"10.1073\/pnas.94.23.12425","article-title":"Prominin, a novel microvilli-specific polytopic membrane protein of the apical surface of epithelial cells, is targeted to plasmalemmal protrusions of non-epithelial cells","volume":"94","author":"Weigmann","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1186\/s13287-022-02937-6","article-title":"Modeling of mitochondrial bioenergetics and autophagy impairment in MELAS-mutant iPSC-derived retinal pigment epithelial cells","volume":"13","author":"Bhattacharya","year":"2022","journal-title":"Stem Cell Res. Ther."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Xu, P., Guo, F., Wang, Y., Chen, G., Song, X., Luo, B.Y., Zheng, D., Gao, G., Yin, W., and Zhang, S. (2026). Exogenous Photoreceptor-Specific N-Glycosylated PROM1 Rescues Retinal Degeneration in Patient and Mouse Models. Mol. Ther., S1525-0016(26)00126-7.","DOI":"10.1016\/j.ymthe.2026.02.040"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"jcs262298","DOI":"10.1242\/jcs.262298","article-title":"prominin-1-null Xenopus laevis develop subretinal drusenoid-like deposits, cone-rod dystrophy and RPE atrophy","volume":"137","author":"Carr","year":"2024","journal-title":"J. Cell Sci."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Chen, H., Luo, Z., Dong, L., Tan, Y., Yang, J., Feng, G., Wu, M., Li, Z., and Wang, H. (2013). CD133\/prominin-1-mediated autophagy and glucose uptake beneficial for hepatoma cell survival. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0056878"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1002\/sctm.17-0223","article-title":"Prominin-1\/CD133: Lipid Raft Association, Detergent Resistance, and Immunodetection","volume":"7","author":"Karbanova","year":"2018","journal-title":"Stem Cells Transl. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1038\/s41421-020-0161-3","article-title":"Emerging roles of ATG proteins and membrane lipids in autophagosome formation","volume":"6","author":"Nishimura","year":"2020","journal-title":"Cell Discov."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"10896","DOI":"10.1073\/pnas.1523145113","article-title":"PtdIns(4,5)P2 signaling regulates ATG14 and autophagy","volume":"113","author":"Tan","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e201912098","DOI":"10.1083\/jcb.201912098","article-title":"A PI3K-WIPI2 positive feedback loop allosterically activates LC3 lipidation in autophagy","volume":"219","author":"Fracchiolla","year":"2020","journal-title":"J. Cell Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"6829","DOI":"10.1073\/pnas.1217002110","article-title":"Activation of PI3K\/Akt pathway by CD133-p85 interaction promotes tumorigenic capacity of glioma stem cells","volume":"110","author":"Wei","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Kharouf, N., Flanagan, T.W., Alamodi, A.A., Al Hmada, Y., Hassan, S.Y., Shalaby, H., Santourlidis, S., Hassan, S.L., Haikel, Y., and Megahed, M. (2024). CD133-Dependent Activation of Phosphoinositide 3-Kinase \/AKT\/Mammalian Target of Rapamycin Signaling in Melanoma Progression and Drug Resistance. Cells, 13.","DOI":"10.3390\/cells13030240"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"3873","DOI":"10.1111\/jcmm.17421","article-title":"STAT3 suppresses the AMPKalpha\/ULK1-dependent induction of autophagy in glioblastoma cells","volume":"26","author":"Bhattacharya","year":"2022","journal-title":"J. Cell Mol. Med."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Zhou, M., Geathers, J.S., Grillo, S.L., Weber, S.R., Wang, W., Zhao, Y., and Sundstrom, J.M. (2020). Role of Epithelial-Mesenchymal Transition in Retinal Pigment Epithelium Dysfunction. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.00501"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"102460","DOI":"10.1016\/j.omtn.2025.102460","article-title":"TMEM97 governs partial epithelial-mesenchymal transition of retinal pigment epithelial cells via the CTNND2-ADAM10 axis","volume":"36","author":"Li","year":"2025","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"507","DOI":"10.7150\/ijbs.30575","article-title":"Autophagy resists EMT process to maintain retinal pigment epithelium homeostasis","volume":"15","author":"Feng","year":"2019","journal-title":"Int. J. Biol. Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e70018","DOI":"10.1111\/acel.70018","article-title":"Activated mTOR Signaling in the RPE Drives EMT, Autophagy, and Metabolic Disruption, Resulting in AMD-Like Pathology in Mice","volume":"24","author":"Chowdhury","year":"2025","journal-title":"Aging Cell"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Wang, N., Wang, Y., Zhang, L., Yang, W., and Fu, S. (2025). Molecular Mechanisms of Epithelial-Mesenchymal Transition in Retinal Pigment Epithelial Cells: Implications for Age-Related Macular Degeneration (AMD) Progression. Biomolecules, 15.","DOI":"10.3390\/biom15060771"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/s11658-025-00732-8","article-title":"Potential of autophagy in subretinal fibrosis in neovascular age-related macular degeneration","volume":"30","author":"Blasiak","year":"2025","journal-title":"Cell Mol. Biol. Lett."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"4500","DOI":"10.1096\/fj.13-236166","article-title":"Lysosomal alkalinization, lipid oxidation, and reduced phagosome clearance triggered by activation of the P2X7 receptor","volume":"27","author":"Guha","year":"2013","journal-title":"FASEB J."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Higashijima, F., Hasegawa, M., Yoshimoto, T., Kobayashi, Y., Wakuta, M., and Kimura, K. (2022). Molecular mechanisms of TGFbeta-mediated EMT of retinal pigment epithelium in subretinal fibrosis of age-related macular degeneration. Front. Ophthalmol., 2.","DOI":"10.3389\/fopht.2022.1060087"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1167\/iovs.66.11.39","article-title":"Yes-Associated Protein (YAP) Is Associated With Disease Severity and Visual Prognosis in Epiretinal Membrane","volume":"66","author":"Yang","year":"2025","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Shu, D.Y., Butcher, E., and Saint-Geniez, M. (2020). EMT and EndMT: Emerging Roles in Age-Related Macular Degeneration. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21124271"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1080\/15548627.2022.2069437","article-title":"Autophagy in age-related macular degeneration","volume":"19","author":"Kaarniranta","year":"2023","journal-title":"Autophagy"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Falcao, A.S., Pedro, M.L., Tenreiro, S., and Seabra, M.C. (2025). Targeting Lysosomal Dysfunction and Oxidative Stress in Age-Related Macular Degeneration. Antioxidants, 14.","DOI":"10.3390\/antiox14050596"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1007\/s00109-015-1275-1","article-title":"Light induces NLRP3 inflammasome activation in retinal pigment epithelial cells via lipofuscin-mediated photooxidative damage","volume":"93","author":"Brandstetter","year":"2015","journal-title":"J. Mol. Med."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/5\/635\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T17:43:50Z","timestamp":1777052630000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/5\/635"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,24]]},"references-count":75,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["biom16050635"],"URL":"https:\/\/doi.org\/10.3390\/biom16050635","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,24]]}}}