SWAP70 (switching B cell complex subunit SWAP70) is a phosphatidylinositol 3,4,5-trisphosphate-dependent guanine nucleotide exchange factor that regulates RAC-mediated signal transduction independently of RAS, controlling actin cytoskeleton dynamics and cell membrane protrusion [UniProt]. The protein is predominantly expressed in B lymphocytes, where it localizes to the cytoplasm in resting cells and translocates to the nucleus and cell membrane upon B-cell activation, potentially participating in signal transduction and heavy-chain class switch recombination 1. Mechanistically, SWAP70 functions as a mechano-responsive regulator of endothelial inflammation through CAV1 (caveolin-1) nuclear translocation under oscillatory shear stress conditions 2. In cardiac tissue, SWAP70 suppresses pathological hypertrophy by inhibiting TAK1-mediated phosphorylation of downstream MAPK signaling pathways 3. Clinically, SWAP70 demonstrates protective associations across multiple cardiovascular conditions. Elevated plasma SWAP70 levels are causally associated with reduced ischemic stroke risk 4, and genetic variation (rs10840293) links SWAP70 to coronary artery disease susceptibility 2. Multi-omics analysis confirms SWAP70 as associated with decreased CAD risk 5. Additionally, fasting-induced changes in SWAP70 levels show putative beneficial effects for rheumatoid arthritis 6. These findings position SWAP70-targeting strategies as promising therapeutic approaches for cardiovascular disease prevention.