CTSW (cathepsin W) is a cysteine protease that functions as a host factor essential for influenza A virus (IAV) entry into cells 1. Mechanistically, CTSW operates specifically at the late endosomal stage of viral entry, where its proteolytic activity is required for escape of viral particles from late endosomes and subsequent viral-endosomal membrane fusion 12. The intracellular pool of CTSW, rather than secreted forms, promotes this antiviral function 2. CTSW cleaves at least 79 potential direct cellular target proteins during infection, with a defined cleavage motif shared among substrates 2. Beyond its antiviral role, CTSW shows clinical relevance in cancer biology. Reduced CTSW expression is associated with poor prognosis in pancreatic ductal adenocarcinoma, functioning as a novel prognostic biomarker 3. In cutaneous T-cell lymphomas, malignant CD8+ and TCR-γδ+ clones express elevated CTSW alongside other cytotoxic markers, correlating with distinct immunophenotypes 4. CTSW knockdown impairs IAV replication across multiple viral subtypes 1, and CTSW-deficient mice show enhanced survival following IAV infection 2, supporting CTSW as a promising host-directed antiviral drug target with potential advantages over virus-targeted approaches due to lower resistance likelihood.