TMPRSS4 (transmembrane protease serine 4) is a type II transmembrane serine protease that plays critical roles in both cancer progression and viral infections 1. The protein functions as a cell surface-associated protease with serine-type peptidase activity, facilitating proteolytic cleavage of various substrates 2. In cancer, TMPRSS4 promotes tumor progression by facilitating epithelial-mesenchymal transition (EMT), leading to increased invasion, migration, and metastasis 3. Mechanistically, TMPRSS4 downregulates E-cadherin while upregulating integrin-α5 and urokinase-type plasminogen activator, activating intracellular signaling pathways including FAK, Src, Akt, and ERK1/2 1. In viral infections, TMPRSS4 facilitates SARS-CoV-2 entry into human small intestinal enterocytes by cleaving viral spike glycoproteins, promoting fusogenic activity 4. Additionally, TMPRSS4 cleaves SIGLEC12 during necroptosis to produce a fragment required for plasma membrane rupture, contributing to this form of programmed cell death 5. Clinically, TMPRSS4 is overexpressed in multiple cancer types including pancreatic, colorectal, gastric, lung, thyroid, and prostate cancers, with elevated expression correlating with poor prognosis 21. These findings establish TMPRSS4 as a potential therapeutic target in both cancer and infectious diseases.