Transmembrane serine protease 3 (TMPRSS3) (TMPRSS3)

Transmembrane serine protease 3 (TMPRSS3) is a member of the type II transmembrane serine protease (TTSP) family, characterized by an extracellular serine protease domain and a transmembrane anchor (UniProt P57727). It is essential for the survival and maintenance of cochlear hair cells and spiral ganglion neurons in the inner ear, where it is thought to regulate sodium homeostasis by activating the epithelial sodium channel (ENaC) (GeneCards; NIH, 2026). Mutations in the TMPRSS3 gene are a leading cause of autosomal recessive nonsyndromic hearing loss, manifesting as either congenital profound deafness (DFNB10) or late-onset progressive hearing loss (DFNB8) (Frontiers in Genetics, 2021). Beyond its role in hearing, TMPRSS3 is frequently overexpressed in various malignancies, including ovarian, breast, and gastric cancers, where it promotes tumor cell proliferation and metastasis through the activation of signaling pathways like ERK1/2 and PI3K/Akt (NIH, 2026; Wikipedia). Therapeutic strategies currently under investigation include AAV-mediated gene therapy (e.g., Myr-201) to restore functional protein in the inner ear and the use of diuretics like furosemide to mitigate hair cell damage by reducing endocochlear potential (Myrtelle, 2022; Hearing Review, 2025). In oncology, TMPRSS3 is being explored as a potential biomarker and therapeutic target for protease inhibition.

Other names

Transmembrane protease serine 3Tumor-associated differentially-expressed gene 12 proteinTADG-12ECHOS1DFNB8DFNB10Serine protease TADG-12

Restoration of functional serine protease activity via gene therapy to promote hair cell survival; reduction of endocochlear potential to prevent hair cell damage; inhibition of protease-mediated signaling pathways in cancer.