CST3 encodes cystatin C, a cysteine protease inhibitor localized to chromosome 20 1. As an endogenous inhibitor of cysteine proteases including cathepsin B and L, CST3 serves critical regulatory functions across multiple physiological systems 2. In pancreatic pathophysiology, CST3 protects against acute pancreatitis by inhibiting intrapancreatic protease cascades, though trypsin-mediated cleavage and allosteric activation of cathepsin B can paradoxically promote disease progression 2. CST3 regulates bone homeostasis through transcriptional control mechanisms, with elevated CST3 expression suppressing osteoclastic differentiation 3. In spermatogenesis, CST3 maintains spermatogonial stem cell homeostasis through autophagy regulation, where dysregulation associates with male infertility 4. The CST3 G73A polymorphism shows ethnicity-dependent associations with Alzheimer's disease risk in Caucasians but not Asians 5. CST3 is elevated in periodontal disease as a compensatory response to excessive proteolytic activity 6, and plasma CST3 levels predict aortic aneurysm/dissection risk up to 10 years prior to clinical diagnosis 7. However, CST3 gene detection is compromised in single-nucleus RNA sequencing of human microglial activation states 8, limiting assessment in neurodegenerative disease contexts.