The cystatin superfamily encompasses proteins that contain
multiple cystatin-like sequences. Some of the members are active
cysteine protease inhibitors, while others have lost or perhaps
never acquired this inhibitory activity. There are three inhibitory
families in the superfamily, including the type 1 cystatins
(stefins), type 2 cystatins and the kininogens. The type 2 cystatin
proteins are a class of cysteine proteinase inhibitors found in a
variety of human fluids and secretions, where they appear to
provide protective functions. The cystatin locus on chromosome 20
contains the majority of the type 2 cystatin genes and pseudogenes.
This gene is located in the cystatin locus and encodes the most
abundant extracellular inhibitor of cysteine proteases, which is
found in high concentrations in biological fluids and is expressed
in virtually all organs of the body. A mutation in this gene has
been associated with amyloid angiopathy. Expression of this protein
in vascular wall smooth muscle cells is severely reduced in both
atherosclerotic and aneurysmal aortic lesions, establishing its
role in vascular disease.
