ARPC5 (actin related protein 2/3 complex subunit 5) is a critical component of the Arp2/3 complex that mediates branched actin network formation essential for cellular processes including motility, phagocytosis, and immune function 1. The protein exists as two paralogous isoforms, ARPC5 and ARPC5L, which exhibit distinct tissue distribution patterns and functional roles 23. ARPC5 is predominantly required for cytoplasmic actin dynamics, while ARPC5L specifically drives nuclear actin polymerization during T cell activation 3. Loss-of-function mutations in ARPC5 cause severe immunodeficiency with autoimmunity and autoinflammation, leading to early mortality due to defective macrophage and neutrophil function 41. ARPC5-deficient immune cells fail to effectively phagocytose and eliminate intracellular bacteria, resulting in microbiota breach of intestinal mucosa and systemic inflammation 1. In cancer contexts, ARPC5 acts as an oncogene, with upregulation promoting cell proliferation, migration, and invasion in prostate cancer and multiple myeloma 56. The protein's expression correlates with poor prognosis in gliomas and is associated with immune infiltration 7. ARPC5's essential role in both developmental processes and immune system function makes it a critical regulator of cellular actin dynamics.