Cystatin D, a predominant type-2 cysteine protease inhibitor in saliva, belongs to the cystatin superfamily of endogenous inhibitors that target endosomal/lysosomal cysteine proteases including cathepsins B, H, L and S. Studies have identified Cystatin D as a potential tumor suppressor gene in colon cancer due to its ability to antagonize the Wnt/β-catenin signaling pathway and repress c-MYC expression, thereby inhibiting cell proliferation. This evidence concerns the gene MYC and colonic neoplasm.