The cystatin superfamily is a well-established family of cysteine protease inhibitors. All true cystatins inhibit cysteine peptidases of the papain family, such as cathepsins, while some also inhibit legumain family enzymes. The CRES (cystatin-related epididymal spermatogenic) protein defines a new subgroup in the family 2 cystatins of the cystatin superfamily. CRES proteins lack two of the three consensus sites necessary for the cystatin inhibition of C1 cysteine proteases. Due to their expression patterns, it is likely that CRES proteins may perform unique and tissue-specific functions in the reproductive and neuroendocrine systems. As a member of the CRES subfamily, Cystatin 9, also designated CLM, is a 159 amino acid protein that is expressed in heart, placenta, lung, liver, skeletal muscle and pancreas. Cystatin 9 is thought to play a role in hematopoietic differentiation or inflammation. It has also been shown to be upregulated by LPS in some cancer cell lines, such as promyelocytic leukemia (HL-60) and myelomonocytic leukemia.