Only recently have studies of human patients shown deficiency of lysosomal aspartyl proteinase cathepsin D. Secreted cathepsin S cleaves some extracellular matrix (ECM) proteins. Nonetheless, these structures contain endocytic markers even small lysosomal proteins such as cathepsin D. Chronologically, action of cathepsin S follows two cleavages performed by aspartyl proteases. These include lactoferrin, elastase, and cathepsin G. The osteoclasts secrete hydrogen ions, collagenase, cathepsin K and hydrolytic enzymes into this compartment. M cells express the protease cathepsin E, similar to other antigen-presenting cells. The expression of cathepsin S can be triggered by proinflammatory factors secreted by tumor cells. An upregulation of cathepsin G was reported in studies of keratoconus. Ulinastatin also prevents tumor progression, partially by inhibiting cathepsin B activity. The expression of cathepsin K in cultured endothelial cells is regulated by shear stress. This sequence can be cleaved by cathepsin C, removing 2 amino acids. Of these hydrolytic enzymes, cathepsin K is of most importance. They act by transactivating cathepsin B promotor activity and inducing its mRNA expression. Overexpression of cathepsin B is correlated with invasive and metastatic cancers.