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Cystatin C (CysC), a cysteine protease inhibitor, has been widely proven to be a highly sensitive biomarker to predict the kidney function. The similarity of the renal and cerebral small vessels has awakened a surge of studies suggesting that CysC plays a key role in various cerebrovascular disorders. This review focuses on four major mechanisms of CysC in a variety of cerebrovascular diseases. (1) The property of the CysC Leu-68-Gln (L68Q) variant to aggregate and the property of the wild type CysC protein to co-aggregate with Amyloid-β (Aβ); (2) The disruption of equilibrium between CysC and related cysteine proteases; (3) The function of CysC as an inflammatory inducing factor; (4) The ability of CysC to induce autophagy. The combination of these CysC properties provides a well-supported novel biomarker for cerebrovascular diseases.