Cystatin C is a cysteine (thiol) protease inhibitor that belongs to the type II cystatin gene superfamily and is the most abundant extracellular inhibitor of cysteine proteases. Cystatin C is a constitutively secreted, amyloidogenic protein, which forms a two-fold symmetric dimer and modulates both cysteine protease activity and the expression of class II MHC molecules. Expression of cystatin C is an indicator of kidney function and glomerular filtration rate. Mutations in the cystatin C gene can lead to protein aggregates, which are implicated in hereditary amyloid angiopathy (HCCAA) and cerebral hemorrhage. Although both wild-type and mutant cystatin C are capable of forming concentration dependent inactive dimers, mutant cystatin C dimerizes at lower concentrations and is more susceptible to serine proteases, which may facilitate aggregation. In neuronal cells, oxidative stress stimulates expression of cystatin C, which may positively regulate apoptosis.
