NOX3 is a membrane-bound NADPH oxidase that catalyzes superoxide generation from molecular oxygen using NADPH as an electron donor, functioning as part of a multi-subunit complex 1. As one of seven mammalian NOX family members, NOX3 shares the fundamental capacity to transport electrons across the plasma membrane and generate reactive oxygen species (ROS) 2. NOX3 is highly expressed in inner ear tissues, where it plays a critical physiological role in otoconia biogenesis—the formation of crystalline gravity-sensing structures essential for vestibular function 1. Loss-of-function mutations in NOX3 result in impaired otoconia development and perturbed vestibular function 3. Beyond the inner ear, NOX3 participates in oligodendrocyte differentiation through ROS-mediated signaling pathways involving PKC and CREB phosphorylation 4. Pathologically, NOX3 activation contributes to inner ear damage, including cisplatin-induced hearing loss and age-related hearing decline 3. Genetic variants in NOX3 have been associated with Meniere's disease susceptibility 5. NOX3-targeted inhibition shows therapeutic promise for protecting hearing function and preventing ototoxicity, though development of specific inner ear-penetrating NOX3 inhibitors remains ongoing 6.