Otopetrin-1 (OTOP1) (OTOP1)

Otopetrin-1 (OTOP1) is a specialized proton-selective ion channel that serves as the primary sensory receptor for sour taste in mammals (Tu et al., 2018; Teng et al., 2019). Located on the apical membrane of sour-sensitive taste receptor cells, OTOP1 mediates the influx of protons in response to acidic stimuli, which triggers cell depolarization and subsequent neural signaling to the brain (Zhang et al., 2019). Beyond its role in gustation, OTOP1 is critically involved in the vestibular system, where it is required for the formation of otoconia—calcium carbonate crystals necessary for sensing gravity and linear acceleration (Hurle et al., 2003). Mutations in the OTOP1 gene lead to vestibular defects, such as the "tilted" phenotype in mice, and are linked to balance disorders in humans (Kim et al., 2011). Recent studies have also identified OTOP1 as a sensor for ammonium chloride and suggested its involvement in metabolic processes within adipose tissue (Liang et al., 2023; Tu et al., 2023). While no OTOP1-targeted drugs are currently approved, the channel is an active area of research for the development of taste modulators and treatments for vestibular dysfunction. Experimental modulators, including small-molecule inhibitors and positive allosteric modulators like MFaN, are being used to explore its therapeutic potential and structural biology (Burendei et al., 2025; Mi et al., 2025).

Other names

OTOP1Otopetrin 1Sour taste receptorProton channel OTOP1

Proton channel inhibition or allosteric activation