CYBB, also known as NOX2 or gp91phox, encodes the catalytic subunit of the phagocyte NADPH oxidase complex, a critical enzyme in the antimicrobial respiratory burst. This transmembrane protein facilitates electron transfer across membranes, generating reactive oxygen species (ROS) to kill pathogens. Mutations in CYBB are linked to X-linked chronic granulomatous disease (X-CGD), an immunodeficiency disorder characterized by impaired microbial clearance and recurrent infections. CYBB antibodies are widely used in research and diagnostics to detect protein expression, assess oxidase complex assembly, and study functional defects in immune cells. They help identify carriers of X-CGD and evaluate gene therapy outcomes. Beyond immunity, CYBB-derived ROS influence redox signaling in non-phagocytic cells, contributing to processes like inflammation, cellular proliferation, and apoptosis. Aberrant CYBB expression has been implicated in cancer progression, vascular pathologies, and autoimmune diseases, making it a potential therapeutic target. Commercial CYBB antibodies target specific epitopes, enabling applications in Western blot, flow cytometry, and immunohistochemistry. Understanding CYBB’s role continues to advance insights into innate immunity, oxidative stress-related diseases, and targeted treatment strategies.