The present study revealed mutations in βA4-crystallin-driven cataractogenesis via distinct mechanisms according to their distinct structural contexts. αA-crystallin functions as a primary mitigator of severe misfolding, preferentially stabilizing aggregation-prone conformers. These findings suggest that mutation-specific stabilization via small-molecule chaperones or enhanced αA-crystallin activity may represent potential precision therapeutic strategies for βA4-crystallin-associated congenital cataracts.
Lin et al. (Fri,) studied this question.