ITGB8 encodes integrin beta-8, a subunit that forms the heterodimer αvβ8 (ITGAV:ITGB8) with specific roles in immune regulation and neurodevelopment. As an RGD-binding integrin, αvβ8 functions as a receptor for fibronectin and mediates TGFβ activation through interaction with latency-associated peptide on cell surfaces 1. In immune contexts, ITGB8 is essential for peripheral regulatory T cell (Treg) differentiation: loss of ITGB8 in intestinal Thetis cells severely impairs pTreg generation and causes colitis 1. ITGB8 also functions in microglia homeostasis, where APOE4-mediated induction of ITGB8-TGFβ signaling impairs disease-associated microglia responses to Alzheimer's disease pathology by upregulating homeostatic checkpoints 2. In human brain development, ITGB8 is specifically upregulated in human radial glia and activates PI3K-AKT-mTOR signaling, contributing to human-specific cortical expansion 3. Genetically, ITGB8 variants are associated with inflammatory bowel disease susceptibility, with disease-risk alleles correlating with increased expression upon immune stimulation 4. Beyond immune regulation, ITGB8 expression supports vasculogenesis and placental blood vessel development. These findings establish ITGB8 as a critical integrator of TGFβ-mediated immune tolerance and neuroinflammatory responses relevant to multiple inflammatory and neurodegenerative diseases.