Generates hydrogen peroxide which is required for the activity of thyroid peroxidase/TPO and lactoperoxidase/LPO. Plays a role in thyroid hormones synthesis and lactoperoxidase-mediated antimicrobial defense at the surface of mucosa. May have its own peroxidase activity through its N-terminal peroxidase-like domain. H(+) + NADH + O2 = H2O2 + NAD(+) H(+) + NADPH + O2 = H2O2 + NADP(+) Peroxidase activity is inhibited by aminobenzohydrazide (By similarity). The NADPH oxidase activity is calcium-dependent. Hormone biosynthesis; thyroid hormone biosynthesis. Heterodimer with DUOXA2; disulfide-linked. Interacts with TXNDC11, TPO and CYBA. Localizes to the apical membrane of epithelial cells. Localizes on internal membrane structures under resting conditions, translocates to the plasma membrane and cell-cell junctions upon challenge with enteric pathogens, such as Escherichia coli. Expressed in colon, small intestine, duodenum and tracheal surface epithelial cells (at protein level). Expressed in thyrocytes. Also detected in kidney, liver, lung, pancreas, prostate, salivary glands, rectum and testis. Widely expressed in fetal tissues. By forskolin, thyrotropin and the Th1-specific cytokine IFNG/IFN-gamma. N-glycosylated. The disease is caused by variants affecting the gene represented in this entry. Defects in DUOX2 may play a role in the pathogenesis of very early onset inflammatory bowel disease (VEOIBD), a chronic, relapsing inflammation of the gastrointestinal tract with a complex etiology diagnosed before 6 years of age. VEOIBD is subdivided into Crohn disease and ulcerative colitis phenotypes. Crohn disease may affect any part of the gastrointestinal tract from the mouth to the anus, but the phenotype of children with onset of Crohn disease occurring younger than the age of 10 is predominantly colonic, with a lower risk of ileal disease. Bowel inflammation is transmural and discontinuous; it may contain granulomas or be associated with intestinal or perianal fistulas. In contrast, in ulcerative colitis, the inflammation is continuous and limited to rectal and colonic mucosal layers; fistulas and granulomas are not observed. Both diseases include extraintestinal inflammation of the skin, eyes, or joints. In the N-terminal section; belongs to the peroxidase family. DUOX2