ARPIN (actin-related protein 2/3 complex inhibitor) is a negative regulator of actin polymerization that functions as a critical controller of cell migration and immune responses. Mechanistically, ARPIN inhibits the actin-nucleating activity of the Arp2/3 complex in competition with nucleation-promoting factors, participating in an incoherent feedforward loop at the lamellipodium tip where it responds to Rac signaling to suppress actin polymerization while Rac simultaneously stimulates polymerization through the WAVE complex 1. This dual regulation allows ARPIN to steer directional cell migration by controlling directional persistence and lamellipodium morphogenesis. Clinically, ARPIN expression is dysregulated in breast cancer, where reduced expression correlates with advanced tumor stage and significantly increased axillary lymph node metastasis 2. Lower ARPIN expression is an independent risk factor for reduced recurrence-free survival in breast cancer patients 2. In immune function, ARPIN is essential for macrophage phagocytosis, localizing to phagosomal sites and facilitating F-actin cup formation and phagosome completion 1. Human rhinovirus 16 specifically downregulates ARPIN expression to impair bacterial uptake and phagocytosis in macrophages 1, suggesting ARPIN serves as a pathogenic target during viral infection. These findings establish ARPIN as a multifunctional actin regulator with important implications for cancer metastasis and innate immunity.