RAC2 is a hematopoietic-specific small GTPase that cycles between active GTP-bound and inactive GDP-bound states to regulate critical immune cell functions 1. As a key component of the phagocyte NADPH oxidase complex, RAC2 mediates superoxide anion production essential for antimicrobial defense 2. The protein controls actin cytoskeleton dynamics, enabling proper neutrophil chemotaxis, cell migration, and phagocytic responses 3. RAC2 mutations cause a spectrum of primary immunodeficiencies depending on their functional impact: constitutively active mutations lead to neonatal severe combined immunodeficiency (SCID), dominant-negative mutations cause leukocyte adhesion deficiency-like disease with defective neutrophil function, while dominant-activating mutations result in combined immunodeficiency with recurrent infections 3. The hyperactivating RAC2E62K mutation paradoxically enhances macrophage-mediated cell cannibalism, contributing to immunodeficiency through aberrant immune cell interactions 4. Functionally, RAC2-deficient neutrophils exhibit impaired chemotaxis, reduced superoxide production, and abnormal cell survival, defining RAC2 as essential for normal myeloid cell function and establishing RAC2 deficiency as a distinct genetic immunodeficiency syndrome 25.