Cystatine

Cystatin, sometimes spelled cystatine, refers to a superfamily of cysteine protease inhibitors that regulate proteolysis in cells and tissues. Members of this family inhibit cysteine proteases such as cathepsins B, L, and S, thereby modulating protein turnover, antigen processing, and extracellular matrix remodeling. The cystatin superfamily is divided into three subfamilies: type 1 cystatins (stefins A and B), which are intracellular and lack a signal peptide; type 2 cystatins, which are secreted or extracellular and contain disulfide bonds; and type 3 cystatins, known as kininogens, which are larger glycoproteins present in plasma. The proteins typically share conserved regions that contribute to protease binding and inhibition.

Cystatins are widely distributed, found in most body fluids and in many tissues. Type 2 cystatins are secreted by various cell types and can act locally or circulate systemically. The cystatin C molecule, encoded by the CST3 gene in humans, is among the best characterized members and is commonly used as a biomarker of kidney function because its clearance from blood is relatively constant and less affected by muscle mass than creatinine.

In clinical and research contexts, cystatins are studied as modulators of inflammation, immune function, and cancer biology. Alterations in cystatin levels or genetic variants can be associated with disease risk, progression, or response to therapy. Cystatin C in particular has been investigated in neurological disease and aging, where its interactions with amyloid proteins and roles in proteostasis are of interest.