ARAP3 is a phosphatidylinositol 3,4,5-trisphosphate-dependent dual GTPase-activating protein that regulates actin cytoskeleton remodeling by inactivating ARF6, RAC1, RHOA, and CDC42 1. The protein is activated upon binding to PI(3,4,5)P3 and PI(3,4)P2 lipids via its N-terminal pleckstrin homology domain, leading to plasma membrane recruitment essential for function 1. ARAP3 undergoes transient tyrosine phosphorylation during cell-matrix adhesion and growth factor stimulation, with phosphorylation at Y1399 and Y1404 acting as negative regulators 2. The protein inhibits cell spreading and RhoA/Rac1 activation through its RhoGAP domain, while interacting with signaling partners including Vav2 and Odin-Sam1 34. Disease relevance includes papillary thyroid carcinoma, where ARAP3 downregulation suppresses cell proliferation, migration, and invasion 5. ARAP3 protects against excessive inflammation-induced microvascular leakage by regulating endothelial cell permeability and neutrophil activation 6. In Alzheimer's disease pathology, reduced ARAP3 levels following PI(3,4)P2-mediated degradation contribute to RhoA hyperactivation and actin cytoskeleton disruption 7. ARAP3 may also participate in angiogenesis regulation relevant to moyamoya disease 8.