The function of TMPRSS2 (transmembrane serine protease 2, ENSG00000184012) is as follows. Plasma membrane-anchored serine protease that cleaves at arginine residues (PubMed:32703818, PubMed:35676539, PubMed:37990007, PubMed:38964328). Participates in proteolytic cascades of relevance for the normal physiologic function of the prostate (PubMed:25122198). Androgen-induced TMPRSS2 activates several substrates that include pro- hepatocyte growth factor/HGF, the protease activated receptor-2/F2RL1 or matriptase/ST14 leading to extracellular matrix disruption and metastasis of prostate cancer cells (PubMed:15537383, PubMed:25122198, PubMed:26018085). In addition, activates trigeminal neurons and contribute to both spontaneous pain and mechanical allodynia (By similarity). {ECO:0000250|UniProtKB:Q9JIQ8, ECO:0000269|PubMed:15537383, ECO:0000269|PubMed:25122198, ECO:0000269|PubMed:26018085, ECO:0000269|PubMed:32703818, ECO:0000269|PubMed:35676539, ECO:0000269|PubMed:37990007, ECO:0000269|PubMed:38964328}. (Microbial infection) Facilitates human coronaviruses SARS- CoV and SARS-CoV-2 infections via two independent mechanisms, proteolytic cleavage of ACE2 receptor which promotes viral uptake, and cleavage of coronavirus spike glycoproteins which activates the glycoprotein for host cell entry (PubMed:24227843, PubMed:32142651, PubMed:32404436, PubMed:33051876, PubMed:34159616, PubMed:35676539, PubMed:37990007). The cleavage of SARS-COV2 spike glycoprotein occurs between the S2 and S2' site (PubMed:32703818). Upon SARS-CoV-2 infection, increases syncytia formation by accelerating the fusion process (PubMed:33051876, PubMed:34159616, PubMed:35676539). Proteolytically cleaves and activates the spike glycoproteins of human coronavirus 229E (HCoV-229E) and human coronavirus EMC (HCoV-EMC) and the fusion glycoproteins F0 of Sendai virus (SeV), human metapneumovirus (HMPV), human parainfluenza 1, 2, 3, 4a and 4b viruses (HPIV). Essential for spread and pathogenesis of influenza A virus (strains H1N1, H3N2 and H7N9); involved in proteolytic cleavage and activation of hemagglutinin (HA) protein which is essential for viral infectivity. {ECO:0000269|PubMed:21068237, ECO:0000269|PubMed:21325420, ECO:0000269|PubMed:23536651, ECO:0000269|PubMed:23966399, ECO:0000269|PubMed:24027332, ECO:0000269|PubMed:24227843, ECO:0000269|PubMed:32142651, ECO:0000269|PubMed:32404436, ECO:0000269|PubMed:32703818, ECO:0000269|PubMed:33051876, ECO:0000269|PubMed:34159616, ECO:0000269|PubMed:35676539, ECO:0000269|PubMed:37990007}. (Microbial infection) Receptor for human coronavirus HKU1- CoV, acts synergistically with disialoside glycans to facilitate the entry of the virus. After binding to cell-surface disialoside glycans, the viral S protein interacts with the inactive form of TMPRSS2 and inhibits its protease activity. {ECO:0000269|PubMed:38964326, ECO:0000269|PubMed:38964328, ECO:0000269|PubMed:38964329}.