However, the proteolytic efficacy of cysteine cathepsins is regulated at all levels of their expression, ultimately by their endogenous inhibitors, the cystatins (http://www.merops.ec.uk).22 Cystatin superfamily comprises two different families, cystatin family (with extracellular cystatins) and stefin family (with intracellular stefins), all these playing a role in cancer progression.17,31 A specific role for lysosomal cathepsins in stem cells biology has not been reported. This evidence concerns the gene CST4 and cancer.