TMPRSS11B is a transmembrane serine protease that functions as a key regulator of metabolic reprogramming and immune suppression in cancer. Primary Function: TMPRSS11B acts as a membrane-bound proteolytic enzyme with extracellular catalytic activity 1. Mechanism: The protein promotes solubilization of Basigin, a chaperone for lactate monocarboxylate transporters (MCT4 and SLC16A1), thereby enhancing lactate export and glycolytic metabolism in cancer cells 12. In pancreatic ductal adenocarcinoma, low TMPRSS11B expression supports reverse Warburg metabolism by increasing lactate uptake through SLC16A1, promoting stemness properties 2. Disease Relevance: TMPRSS11B is upregulated in lung squamous cell carcinoma (LUSC) where high expression correlates with poor survival in non-small cell lung cancer patients 1. The enzyme promotes acidification of the tumor microenvironment and recruits immunosuppressive M2-like macrophages, creating an immunologically hostile niche 34. Additionally, TMPRSS11B is identified as a key regulatory gene in asthma exacerbation pathogenesis 5 and differentially expressed between idiopathic pulmonary fibrosis and lung squamous cell carcinoma 6. Clinical Significance: TMPRSS11B depletion significantly reduces tumor burden in immunocompetent mouse models and restores immune cell infiltration, nominating this enzyme as a promising therapeutic target for LUSC and potentially other malignancies 34.