CRYAA encodes α-crystallin A, a lens structural protein essential for ocular transparency and refractive function. The protein maintains lens clarity by contributing to the lens refractive index and forms intermediate filaments together with BFSP1 and BFSP2. Beyond its structural role, oxidized α-crystallin acts as a molecular chaperone, preventing protein aggregation under diverse stress conditions including heat and oxidative damage. Pathogenic CRYAA variants cause autosomal dominant congenital and anterior polar cataracts, often accompanied by microcornea, corneal opacity, and iris coloboma. Missense mutations such as R116H 1 and R12L 2 impair protein solubility and promote pathological aggregation in lens epithelial cells. Clinical variability within families carrying identical mutations suggests modifying genetic or environmental factors influence disease manifestation 1. A meta-analysis found that the rs7278468 polymorphism is associated with significantly decreased cataract risk 3. Beyond the lens, emerging evidence indicates CRYAA has therapeutic potential in retinal disease. Exogenous α-crystallin attenuates ischemia-reperfusion injury by activating the Nrf2/HO-1 antioxidant pathway 4 and protects retinal pigment epithelium by suppressing miR-155-5p and activating the SIRT1-PI3K/AKT survival pathway 5. These chaperone and cytoprotective functions position CRYAA as a target for protein-replacement or pathway-modulation approaches in retinal degenerative and ischemic disorders.