| Arp3, encoded by ACTR3, is a highly conserved actin-related protein that functions as a core subunit of the Arp2/3 complex, a seven-member actin nucleation machinery that generates branched actin filament networks required for dynamic cytoskeletal remodeling. Within the complex, Arp3 cooperates structurally with Arp2 and accessory ARPC subunits to form a template that initiates daughter filament assembly from the side of pre-existing actin filaments, producing characteristic branched networks that support membrane protrusion, intracellular trafficking, and cortical actin organization. Activation of the Arp2/3 complex requires nucleation-promoting factors such as WASP, N-WASP, WAVE, WASH, and WHAMM, whose C-terminal WCA domains bind both actin monomers and the Arp2/3 complex to induce conformational rearrangements that reposition Arp2 and Arp3 into an actin-like dimeric configuration competent for filament nucleation. Arp3-dependent actin branching operates downstream of Rho family GTPases including Cdc42 and Rac1, linking extracellular stimuli to rapid cytoskeletal reorganization during lamellipodia formation, chemotaxis, endocytosis, vesicle trafficking, and phagocytosis. Interaction of N-WASP with Cdc42 stimulates localized Arp2/3 activation at the plasma membrane, whereas WAVE complexes couple Rac signaling to broad lamellipodial actin assembly that drives directional migration. Arp3-containing complexes also participate in membrane trafficking pathways involving endosomes, Golgi-associated transport, and clathrin-mediated endocytosis through coordinated recruitment of cortactin and additional actin regulatory proteins that stabilize branched filament junctions. Inactive Arp2/3 maintains Arp2 and Arp3 in a separated arrangement, while activation induces a major conformational transition that aligns these subunits into a filament-like nucleus capable of supporting barbed-end elongation and branch stabilization. Arp3-regulated actin dynamics are essential for immune cell activation, neuronal morphology, epithelial organization, and pathogen-driven actin remodeling, with disruption of Arp2/3 signaling linked to defective leukocyte migration, impaired vesicular transport, and abnormal cell polarity. Dysregulated Arp3 activity is also associated with invasive tumor behavior and metastatic progression through persistent activation of branched actin assembly pathways that enhance cellular motility and matrix invasion, while altered regulation of WASP-family proteins contributes to immunological disorders such as Wiskott-Aldrich syndrome characterized by defective actin-dependent immune responses. |