SH3BP1 is a GTPase-activating protein (GAP) that inactivates Rho-family GTPases, particularly RAC1 and CDC42, converting them from their active GTP-bound to inactive GDP-bound states 12. In cell migration, SH3BP1 spatiotemporally regulates RAC1 activity at the leading edge to control protrusion organization 1. During epithelial junction formation, SH3BP1 forms a complex with JACOP/paracingulin and CD2AP to confine CDC42 activity and coordinate actin remodeling through CapZ 2. SH3BP1 functions in phagocytosis of large particles through PI3K-dependent recruitment to particle engagement sites, where it inactivates RAC1/CDC42 to facilitate actin reorganization and engulfment. In angiogenesis and semaphorin-plexin signaling, SH3BP1 dissociates from PLXND1 upon SEMA3E binding and inactivates RAC1, triggering actin cytoskeleton reorganization and cell collapse 3. Clinically, SH3BP1 dysregulation associates with multiple malignancies. In hepatocellular carcinoma, elevated SH3BP1 promotes metastasis through RAC1-WAVE2 signaling and predicts poor prognosis 45. Similarly, in cervical cancer, high SH3BP1 correlates with enhanced migration, invasion, and cisplatin chemoresistance via RAC1-WAVE2 pathway activation 6. In chr22 myeloid leukemia, SH3BP1 activation through the Cobll1/PACSIN2 interaction promotes TKI resistance and blast crisis progression 7. Conversely, in gastric cancer and acute myeloid leukemia, SH3BP1 functions as a tumor suppressor, with elevated expression correlating with enhanced CD8+ T-cell immunity and reduced progression 89. These context-dependent roles suggest SH3BP1 as a potential therapeutic target across multiple cancer types.