Of all the gene products associated with deafness, transmembrane protease serine 3 is the only enzyme identified so far. The gene coding for this protein, TMPRSS3, is located on chromosome 21, and defines the DFNB8 and DFNB10 critical region associated with inherited hearing loss. The TMPRSS3 gene is expressed in the spiral ganglion, the cells supporting the organ of corti, stria vascularis, thymus, stomach, and testis. The protein is seen to localize in the endoplasmic reticulum.
Although the specific nature of the gene product is not known, there are indications to support the theory that the protease plays a part in the action of the sensory hair cells. The hair cells require an endolymph with high potassium and low sodium concentrations for their proper functioning; an ionic environment maintained by the epithelial amiloride-sensitive sodium channel (ENaC). TMPRSS3 activates the ENaC sodium channel, thereby allowing efficient sodium re-absorption in the inner ear.