EROS protein: Decoding its pivotal role in redox homeostasis and disease pathogenesis

• EROS is a critical chaperone for NADPH oxidase 2 (NOX2) maturation and stability. • Novel structural insights reveal how EROS orchestrates redox signaling and prevents spontaneous activation. • EROS dysfunction is a key mechanism in diseases like chronic granulomatous disease and cancers. • The review explores therapeutic strategies targeting EROS-dependent pathways in pathogenesis. The Essential for Reactive Oxygen Species (EROS) protein, a critical molecular chaperone for NADPH oxidase 2 (NOX2/gp91 phox ), has emerged as a central regulator of redox signaling and immune defense. Recent structural and functional studies reveal that EROS orchestrates NOX2 maturation, prevents spontaneous activation, and regulates reactive oxygen species (ROS) production. Dysfunction of EROS is implicated in chronic granulomatous disease (CGD), cancers and vascular pathologies. This review integrates structural insights into EROS-NOX2 interactions, discusses its dual roles in maintaining redox equilibrium and triggering oxidative stress, and explores therapeutic strategies targeting EROS-dependent pathways. EROS orchestrates NOX2 maturation and redox balance. Its dysfunction fuels disease, offering novel therapeutic targets.