NCF2 (neutrophil cytosolic factor 2) is a critical subunit of the phagocyte NADPH oxidase complex that catalyzes electron transfer from cytosolic NADPH to molecular oxygen, generating superoxide anion (O2−) 12. In this complex, electrons are sequentially transferred from NADPH to flavin adenine dinucleotide (FAD) and then via heme molecules to oxygen through an outer-sphere reaction 2. Activation requires phosphorylation-dependent assembly of cytosolic subunits with the core membrane-bound complex 2. NCF2 dysfunction causes chr1 granulomatous disease (CGD), an autosomal recessive phagocytic disorder characterized by defective intracellular microbial killing and recurrent infections with bacteria and fungi 34. Beyond canonical NADPH oxidase function, NCF2 participates in inflammasome regulation by cooperating with NCF1 and NCF4 to promote NLRP3 and AIM2 inflammasome activation, functioning as an ROS sensor 5. Emerging evidence reveals NCF2's involvement in pathologic conditions. In atherosclerosis, elevated NCF2 correlates with oxidative stress and macrophage ferroptosis 6. NCF2 drives esophageal squamous cell carcinoma progression through ROS-independent mechanisms via the NR2F2/LATS2/YAP1 axis 7. In chemotherapy-induced alopecia, S100A8-mediated NCF2/NOX2 activation promotes ferroptosis in hair follicles 8. NCF2 also regulates neutrophil extracellular trap formation in osteoporosis pathogenesis 9, and serves as a protective factor in ulcerative colitis 10.