The otopetrins are a group of proteins evolutionarily conserved among metazoan []. In most vertebrates there are three Otopetrin genes that encode three proteins, OTOP1, OTOP2, and OTOP3. All form proton-selective ion channels that allow influx of protons into cells []. The structure of otopetrin-1 () shows it to have 12 transmembrane domains, with three conserved sub-domains (OD-1 to OD-III) [, , ]. Otopetrins were initially thought to modulate calcium homeostasis and influx of calcium in response to extracellular ATP []but were subsequently shown to form proton-selective ion channels []. The otopetrins are required for normal formation of otoconia/otoliths in the inner ear. Otoconia are minute biomineral particles embedded in a gelatinous membrane that overlies the sensory epithelium in the inner ear. Gravity and acceleration cause the octoconia to deflect the stereocilia of sensory hair cells. Otoconia are required for normal processing of information regarding spatial orientation and acceleration []. OTOP1 also functions as a receptor for sour taste in mice [, ].
