TMPRSS11F (transmembrane serine protease 11F), also known as human airway trypsin-like protease 4 (HAT-L4), is a type II transmembrane serine protease expressed as a 48-kDa protein on the cell surface 1. The gene encodes a membrane-anchored serine protease that cleaves extracellular substrates including proteins, hormones, growth factors, and extracellular matrix molecules to regulate epithelial function 2. In normal physiology, TMPRSS11F is abundantly expressed in epithelial cells and exocrine glands of skin, esophagus, trachea, and other tissues 1. It plays a critical role in epidermal barrier function, as TMPRSS11F knockout mice demonstrate increased trans-epidermal body fluid loss and elevated neonatal mortality, indicating its importance in maintaining barrier integrity 1. Clinically, TMPRSS11F has relevance in multiple disease contexts. It was identified as part of a prognostic gene signature for lung adenocarcinoma, where it contributes to risk stratification and survival prediction 3. Additionally, TMPRSS11F supports SARS-CoV-2 viral entry across multiple variants including Omicron subvariants, with overexpression enhancing viral entry and syncytium formation 4. In acute myeloid leukemia, ectopic TMPRSS11F expression in neutrophils and monocytes promotes cancer cell invasion and is associated with poor prognosis 5.