CRYBA4 encodes crystallin beta A4, a dominant structural protein of the vertebrate eye lens essential for lens transparency 1. As a member of the beta-crystallin family, CRYBA4 maintains lens clarity through precise protein-protein interactions, particularly with CRYBB2, and is expressed from bidirectional promoters with CRYBB1 during lens fiber differentiation 2. CRYBA4 is located on chromosome 22.2-q13.1 3. Mutations in CRYBA4 cause autosomal dominant congenital cataracts through protein misfolding and reduced monomer stability. The pathogenic c.317T>C mutation (Phe94Ser) destabilizes the crystallin monomer, impairing critical lens protein associations 1. A c.225G>T mutation (Gly64Trp) associates with congenital cataract and microcornea 4. Beyond cataracts, CRYBA4 variants link to microphthalmia, with the Leu69Pro mutation disrupting beta-sheet structure 1. Genetically, CRYBA4 polymorphisms contribute to high myopia susceptibility. The rs2009066 SNP showed significant association with high myopia in Chinese populations (meta-analysis P=1.54e-5, OR=1.41) 56. Additionally, CRYBA4 expression responds to mechanical stress and estrogen signaling in tendon cells, suggesting broader roles beyond the eye 7. CRYBA4 expression increases in male diabetic retinas, indicating potential involvement in diabetic retinopathy pathogenesis 8.