Transmembrane protease serine 3 (TMPRSS3) (TMPRSS3)

Transmembrane protease serine 3 (TMPRSS3) is a type II transmembrane serine protease (TTSP) that is essential for the development and maintenance of the inner ear [2, 4, 16]. It is primarily expressed in the cochlea, where it is thought to regulate the epithelial sodium channel (ENaC) to maintain sodium ion homeostasis in the endolymph, a process critical for the survival of hair cells and spiral ganglion neurons [2, 7, 13, 15]. Mutations in the TMPRSS3 gene are a significant cause of autosomal recessive nonsyndromic hearing loss, presenting as either congenital profound deafness (DFNB10) or late-onset progressive hearing loss (DFNB8) [1, 8, 16]. Beyond its role in the auditory system, TMPRSS3 is frequently overexpressed in various malignancies, including ovarian, breast, and pancreatic cancers, where it contributes to tumor invasion and metastasis [3, 4, 6]. Therapeutic development for TMPRSS3-related conditions includes AAV-mediated gene therapy to restore hearing and the potential use of diuretics like furosemide (Lasix) to prevent hair cell damage by reducing endocochlear potential [1, 10, 12]. In oncology, it serves as a prognostic biomarker and a potential target for protease inhibitors [4, 6].

Other names

Transmembrane serine protease 3Serine protease TADG-12Tumor-associated differentially-expressed gene 12 proteinDFNB8DFNB10ECHOS1TADG12

Gene replacement therapy; Reduction of endocochlear potential