Dual oxidase 2 (DUOX2)

Dual oxidase 2 (DUOX2) is a large transmembrane enzyme predominantly expressed in the thyroid gland, as well as in salivary glands, the digestive tract, and respiratory epithelia[3][1]. It generates hydrogen peroxide (H₂O₂) at the apical membrane of thyroid follicular cells, which is essential for thyroid peroxidase-catalyzed oxidation of iodide and synthesis of thyroid hormones (triiodothyronine/T₃ and thyroxine/T₄)[1][3][5]. DUOX2 contains a peroxidase-like extracellular domain, seven transmembrane domains, two intracellular EF-hand calcium-binding motifs, and cytosolic binding sites for FAD and NADPH[1][4]. Genetic mutations in DUOX2 can lead to insufficient H₂O₂ production, causing transient or permanent congenital hypothyroidism, often associated with goiter and classified as thyroid dyshormonogenesis[3][4]. Outside the thyroid, DUOX2’s H₂O₂ production is implicated in host defense and mucosal immunity[1][5]. There are currently no approved drugs directly targeting DUOX2, but the enzyme’s central role in thyroid dysfunction and ROS biology makes it a subject of ongoing research in endocrinology and redox-related pathologies.

Other names

ThOX2LNOX2P138-TOXNADPH thyroid oxidase 2Large NOX 2Long NOX 2NADH/NADPH thyroid oxidase p138-toxNADPH oxidase/peroxidase DUOX2Thyroid oxidase 2dual oxidase-like domains 2flavoprotein NADPH oxidasep138 thyroid oxidaseNOXEF2TDH6

Inhibitors would act by reducing H₂O₂ generation, thus modulating ROS-dependent signaling or impeding hormone synthesis (investigational).