Transmembrane protease serine 2 (TMPRSS2) (TMPRSS2)

Transmembrane protease serine 2 (TMPRSS2) is a cell surface-anchored enzyme belonging to the type II transmembrane serine protease (TTSP) family, predominantly expressed in the epithelial tissues of the prostate, lungs, and gastrointestinal tract [2, 10, 12]. It plays a vital role in physiological processes by cleaving specific substrates, such as the epithelial sodium channel (ENaC) and pro-hepatocyte growth factor, thereby regulating ion transport and cellular signaling [6, 16, 18]. TMPRSS2 is most notably recognized as a critical host factor for the entry of various respiratory viruses, including SARS-CoV-2 and influenza, where it proteolytically primes viral glycoproteins to enable membrane fusion with the host cell [1, 11, 13]. In the context of oncology, the TMPRSS2 gene frequently undergoes chromosomal translocation with the ERG oncogene, creating a fusion product that drives androgen-dependent progression in a significant portion of prostate cancers [2, 9, 14]. Because of its essential role in viral pathogenesis and cancer, TMPRSS2 is a major therapeutic target, with inhibitors like camostat and nafamostat mesylate being investigated to block viral entry and tumor metastasis [3, 7, 8, 12]. While TMPRSS2-deficient mice appear healthy, suggesting that its inhibition may be well-tolerated, the development of highly selective inhibitors remains a key challenge for clinical application [5, 13, 14].

Other names

PRSS10EpitheliasinSerine protease 10PP9284Transmembrane serine protease 2

Inhibition of serine protease activity to prevent the proteolytic priming of viral glycoproteins or the activation of oncogenic substrates.