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We examined the effects of the R188C mutation on \u03b2B2\u2010crystallin's structural stability and resistance to environmental stressors using purified proteins and cellular models. The \u03b2B2\u2010R188C mutant showed poor stability and a tendency to aggregate under physiological and pathological conditions. The mutation disrupted the oligomerization equilibrium, causing dissociation of dimers into monomers. Molecular dynamics simulations and spectroscopic experiments revealed abnormal protein folding induced by the R188C mutation, increasing susceptibility to environmental stressors. Aggregation was observed in both prokaryotic and eukaryotic models under normal conditions, with enhanced severity under environmental stressors. Notably, lanosterol treatment or \u03b1B\u2010crystallin partially reversed aggregation. In summary, the R188C mutation promotes abnormal aggregation by destabilizing \u03b2B2\u2010crystallin and disrupting oligomerization equilibrium, potentially leading to cataract formation. Targeting aggregate formation with small molecules like lanosterol or enhancing molecular chaperone activity offers a promising strategy for cataract prevention and treatment.<\/jats:p>","DOI":"10.1002\/exp.20240192","type":"journal-article","created":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T10:12:22Z","timestamp":1743588742000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Cataract\u2010Causing Mutant R188C of \u03b2B2 Crystallin With Low Structural Stability is Sensitive to Environmental Stresses and Prone to Aggregates Formation"],"prefix":"10.1002","volume":"5","author":[{"given":"Yibo","family":"Yu","sequence":"first","affiliation":[{"name":"Eye Center of Second Affiliated Hospital, School of Medicine Zhejiang University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silong","family":"Chen","sequence":"additional","affiliation":[{"name":"Eye Center of Second 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