Cathepsin W (CTSW)

Cathepsin W (CTSW) is a papain-like cysteine protease and a member of the cathepsin family, with high substrate and structural specificity. Its expression is predominantly restricted to cytotoxic lymphocytes—namely natural killer (NK) cells and CD8+ T cells—where it is associated with the endoplasmic reticulum and involved in the regulation of cytolytic activity and the immune response. CTSW is also strongly upregulated in peripheral regulatory T cells (pTreg) under TGF-β stimulation, playing a negative regulatory role in pTreg differentiation by cleaving CD25 and limiting IL-2 signal transduction, which calibrates immune tolerance, especially at mucosal sites. CTSW has been implicated as a potential therapeutic target in several disease contexts, notably in cancer for its role in modulating immune cell activity within the tumor microenvironment, and in intestinal inflammation for its control over regulatory T cell differentiation. In infectious disease, CTSW is identified as necessary for influenza A virus (IAV) replication, suggesting its inhibition may offer antiviral benefits. No approved drugs specifically target CTSW, but protease inhibitors and experimental agents are under investigation. Safety concerns with targeting CTSW would likely center around immune suppression and the risk of affecting immune homeostasis due to its crucial role in cytotoxic lymphocyte and regulatory T cell function.

Other names

Cathepsin WCTSWLymphopainLYPNcathepsin Wlymphopain

Inhibitors act by blocking the cysteine protease activity of cathepsin W, thereby reducing its enzymatic cleavage of substrates involved in immune or viral processes.