ARAP1 is a phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating protein that regulates actin cytoskeleton dynamics by controlling ARF and RHO family GTPases. The protein contains multiple functional domains (RhoGAP, ankyrin repeats, and PH domain) that enable its activation by PtdIns(3,4,5)P3 binding and direct regulation of ARF family members, particularly ARF1 and ARF5. ARAP1 promotes macropinocytosis through positive regulation of circular dorsal ruffles and coordinates endosomal trafficking, including EGFR internalization and lysosomal protein recruitment. In retinal pigment epithelium, ARAP1 is essential for photoreceptor survival via its role in outer segment phagocytosis 1; loss-of-function mutations cause photoreceptor degeneration. In bone, ARAP1 regulates osteoclast function through podosome organization and bone-resorption activity. Clinically, ARAP1 variants associate with metabolic and inflammatory conditions. The ARAP1 rs1552224 locus is associated with type 2 diabetes risk, and recent evidence suggests it modulates insulin secretion and glucose homeostasis 2. ARAP1 dysregulation also links to diabetic kidney disease, where the ARAP1-AS2/ARAP1 axis promotes epithelial-mesenchymal transition through Cdc42 and EGFR signaling 34. In cancer contexts, aberrant ARAP1 expression and its antisense transcript ARAP1-AS1 promote macropinocytic nutrient uptake and malignant progression in hepatocellular and other solid tumors 5. Genome-wide association studies implicate ARAP1 in Alzheimer disease pathogenesis in African American individuals via associations with brain β-amyloid burden 6.