TMPRSS11A is a type II transmembrane serine protease expressed on airway epithelial cells and skin tissue that functions in viral activation and cellular senescence regulation. Mechanistically, TMPRSS11A undergoes intracellular autoactivation through autocatalysis before reaching the cell surface 1, distinctly differing from extracellular activation mechanisms in other proteases. The enzyme cleaves and activates viral spike proteins including influenza A virus hemagglutinin and SARS-CoV-2 spike protein 21, with expression in tracheal epithelium suggesting roles in respiratory viral pathogenesis. Notably, TMPRSS11A activation is insensitive to blockade by the cellular inhibitor HAI-1 2, contrasting with related proteases. In aging-related processes, TMPRSS11A levels increase with age in skin and gingival tissue, promoting cellular senescence and inhibiting cell migration through integrin β1 interaction 3. Overexpression decreases cell migration and induces G1 cell cycle arrest. TMPRSS11A shows tissue-specific roles, where downregulation improves wound healing in aged skin but not skeletal muscle 3. Clinically, TMPRSS11A polymorphisms (rs353163 and rs977728) associate with COVID-19 severity; carriers of mutant alleles show increased risk with elevated inflammatory markers including CRP and D-dimer 4. However, in Ukrainian populations, TMPRSS11A rs353163 alone showed no significant association with COVID-19 severity 5. The protein appears dispensable for normal development and health under standard conditions 6.