CRYBA1 encodes βA3/A1-crystallin, which serves dual functions as both a structural lens protein and a regulator of cellular homeostasis. As a major lens component, βA3/A1-crystallin contributes to lens transparency and refractivity essential for vision 1. Beyond the lens, this protein is expressed in retinal astrocytes and retinal pigment epithelial (RPE) cells, where it plays a critical role in lysosomal acidification through interaction with V-ATPase, the proton pump responsible for endolysosomal acidification 1. Loss of functional βA3/A1-crystallin impairs autophagy and phagocytosis in RPE cells, leading to accumulation of undigested cargo in phagolysosomes and pathological changes resembling age-related macular degeneration 1. In astrocytes, βA3/A1-crystallin deficiency causes endolysosomal signaling defects that impair mTOR and Notch/STAT3 pathways, contributing to persistent fetal vasculature disease through abnormal vascular remodeling 2. Mutations in CRYBA1 cause autosomal dominant congenital cataracts, with the recurrent ΔG91 deletion being particularly common in Chinese families, representing a mutational hotspot 34. Interestingly, CRYBA1 overexpression can rescue autophagy defects and restore RPE integrity in AMD-like pathology, suggesting therapeutic potential 5.