ITGAV (integrin subunit alpha V) encodes a transmembrane glycoprotein that heterodimerizes with beta integrins to mediate cell-matrix adhesion, cell migration, and signaling. The protein binds extracellular matrix components including fibronectin and serves as a coreceptor for growth factors such as fibroblast growth factor and IGF-1. ITGAV is essential for normal development; biallelic loss-of-function variants cause eye and brain abnormalities, inflammatory bowel disease, and immune dysregulation 1. At the population level, this gene is LoF-tolerant; however, clinical pathogenicity is distinct from population constraint and emerges in disease contexts. ITGAV functions critically in fibrotic diseases by enabling activation of latent TGF-β through WNT5A/JNK/ROCK signaling 2, and Runx2-mediated upregulation of ITGAV promotes hepatic stellate cell activation in liver fibrosis 3. In pancreatic ductal adenocarcinoma, the POSTN-ITGAV/ITGB5 ligand-receptor axis promotes tumor progression via PI3K/AKT/β-catenin signaling and epithelial-mesenchymal transition 4. ITGAV also associates with early pathophysiological changes in Parkinson's disease, with decreased plasma levels present years before symptom onset 5, and emerges as a causal target in calcific aortic valve disease 6. Multiple integrin antagonists targeting ITGAV—including cilengitide, abciximab, and abituzumab—are approved or in clinical development. Cilengitide treatment prevents radiation-induced pulmonary fibrosis by inhibiting αV integrin-mediated TGF-β activation 7, and microRNA-3606-3p suppresses skin fibrosis by targeting ITGAV alongside GAB1 and TGFBR2 8.