DUOX2

DUOX2 (dual oxidase 2) is a member of the NADPH oxidase family that generates hydrogen peroxide (H₂O₂), a reactive oxygen species required for specialized epithelial functions and thyroid hormone biosynthesis^[1][2]. Mechanistically, DUOX2 supplies H₂O₂ to thyroid peroxidase (TPO), enabling iodination and coupling reactions during thyroxine and triiodothyronine production, making DUOX2 a central component of thyroid hormonogenesis^[1][2][3]. Beyond the thyroid, DUOX2 is highly expressed in gastrointestinal epithelia, where controlled H₂O₂ production contributes to mucosal homeostasis, host defense, and redox-dependent signaling pathways^[1][4]. In disease settings, loss-of-function variants in DUOX2 impair H₂O₂ generation and disrupt thyroid hormone synthesis, causing congenital hypothyroidism and thyroid dyshormonogenesis^[3][5]. Experimental and genetic studies further associate defective DUOX2 activity with intestinal inflammatory disorders, including inflammatory bowel disease and Crohn’s disease, highlighting its importance in epithelial barrier function and immune regulation^[4][6]. Compared with the closely related isoform DUOX1, DUOX2 plays the dominant role in thyroid H₂O₂ generation and is the principal DUOX isoform expressed throughout the gastrointestinal tract, whereas DUOX1 is more strongly associated with airway epithelial biology^[1][4][7]. For experimental applications, DUOX2 is frequently investigated through genetic manipulation or disease-associated variants that alter H₂O₂ production, providing useful models for studying redox signaling, thyroid dysfunction, mucosal immunity, and epithelial inflammatory mechanisms^[1][5][6].