Cystatin-B

Cystatin-B (CSTB) is a small intracellular thiol proteinase inhibitor that reversibly and tightly binds cathepsins L, H, and B, thereby regulating cysteine protease activity (UniProt: P04080). The protein functions as a critical regulator of proteolytic processes within cells, controlling the activity of enzymes involved in cellular protein degradation and remodeling.

CSTB is primarily associated with progressive myoclonic epilepsy type 1 (EPM1), a rare autosomal recessive neurological disorder characterized by stimulus-sensitive myoclonus, seizures, and progressive neurodegeneration with cognitive decline (UniProt: P04080). Mutations in CSTB impair its inhibitory function, leading to dysregulated cathepsin activity and neuronal dysfunction.

In Alzheimer's Disease, CSTB shows disease-relevant elevation in post-mortem AD brain tissue compared to age-matched controls (Chaparral AD proteomics). The protein is significantly upregulated with a mean log2 fold-change of 1.67, suggesting increased protease inhibition may reflect compensatory responses to altered proteolytic balance in AD neurodegeneration or accumulation of protease-resistant aggregates characteristic of the disease.