COL8A2 encodes collagen type VIII alpha-2 chain, a critical extracellular matrix component of Descemet's membrane in the corneal endothelium and vascular endothelia 1. It serves as a major structural component conferring tensile strength to basement membranes and is necessary for maintaining corneal transparency and endothelial barrier function 2. Mechanistically, COL8A2 activation enhances corneal endothelial cell (CEC) function through the HIPPO/YAP signaling pathway and mitochondrial regulation 3. COL8A2 promotes wound healing, increases mitochondrial membrane potential and ATP production, and strengthens transendothelial electrical resistance by modulating actin cytoskeleton architecture 3. Conversely, COL8A2 repression reduces cell viability, proliferation, and mitochondrial function while promoting fibroblast-like transformation 2. COL8A2 mutations are strongly associated with Fuchs endothelial corneal dystrophy (FECD) and posterior polymorphous dystrophy 4. Pathogenic mutations (L450W, Q455K) trigger unfolded protein response activation and altered autophagy in CECs, leading to progressive endothelial degeneration 4. COL8A2 variants also associate with thin central corneal thickness in glaucoma patients 1. However, COL8A2 mutations are not implicated in keratoconus pathogenesis 5. Clinically, COL8A2 represents a therapeutic target for corneal dystrophies; gene activation may restore endothelial cell function and prevent vision-threatening corneal opacification.