Cystatin C is a disease‐associated protein subject to multiple regulation

Xu, Yuekang; Ding, Ying; Li, Xinchen; Wu, Xiaobing

A protease inhibitor, cystatin C (Cst C), is a secreted cysteine protease inhibitor abundantly expressed in body fluids. Clinically, it is mostly used to measure glomerular filtration rate as a marker for kidney function due to its relatively small molecular weight and easy detection. However, recent findings suggest that Cst C is regulated at both transcriptional and post‐translational levels, and Cst C production from haematopoietic cell lineages contributes significantly to the systematic pools of Cst C. Furthermore, Cst C is directly linked to many pathologic processes through various mechanisms. Thus fluctuation of Cst C levels might have serious clinical implications rather than a mere reflection of kidney functions. Here, we summarize the pathophysiological roles of Cst C dependent and independent on its inhibition of proteases, outline its change of expression by various stimuli, and elucidate the regulatory mechanisms to control this disease‐related protease inhibitor. Finally, we discuss the clinical implications of these findings for translational gains.