ITGA5 (integrin subunit alpha 5) encodes a transmembrane adhesion receptor that mediates cell-cell and cell-substrate interactions through binding to fibronectin and participation in focal adhesion signaling. The protein functions in wound healing, cell spreading, angiogenesis, and integrin-mediated signaling pathways including FAK/PI3K/AKT and TGF-β cascades. ITGA5 is implicated in multiple malignancies through its role in tumor cell-stromal interactions and immune evasion. In triple-negative breast cancer, elevated circRPPH1 promotes ITGA5 expression to activate FAK/PI3K/AKT signaling and tumor progression 1, while LOX-mediated ITGA5 upregulation drives chemoresistance that can be reversed by targeting the HIF-1α/LOX/ITGA5 axis 2. In glioblastoma, ITGA5 mediates immune escape by activating TGF-β signaling in glioblastoma stem cells 3 and by promoting mesenchymal differentiation and immunosuppressive macrophage formation through exosomal protein delivery, with ITGA5 blockade enhancing anti-PD-1 efficacy 4. In hepatocellular carcinoma, myofibroblast-derived extracellular vesicles transfer ITGA5 to tumor cells, augmenting cancer stem cell properties and reducing PD-L1 treatment response 5. In non-small-cell lung cancer, integrin αVβ1-activated PYK2 signaling downstream of ITGA5 promotes tumor progression 6. ITGA5-expressing tumor cells also interact with peripheral nerves to suppress natural killer cell function through nerve growth factor secretion, with cilengitide improving immunotherapy efficacy 7. Clinically, ITGA5-targeting agents including ATN-161 and VOLOCIXIMAB represent therapeutic approaches to overcome immune resistance and enhance checkpoint inhibitor efficacy. Additionally, 13-methylpalmatine alleviates idiopathic pulmonary fibrosis by suppressing the ITGA5/TGF-β/Smad pathway 8.