Calpain small subunit 1

Calpain small subunit 1 (CAPNS1, also called CSS1) is the regulatory subunit of calpain, a calcium-activated intracellular protease (UniProt: P04632). It functions as an essential cofactor enabling limited proteolysis of substrates involved in cytoskeletal reorganization and cell signaling pathways. The protein is 268 amino acids in length with a molecular mass of approximately 28 kDa.

CAPNS1 is broadly expressed and has been associated with primary pulmonary hypertension (PPH6, MIM 620777) in the UniProt disease database, but its primary roles relate to calcium-dependent protease regulation in multiple cell types including neurons (UniProt: P04632). Calpains are known to participate in neuronal plasticity, dendritic spine dynamics, and axonal degeneration pathways relevant to neurological disease.

In Alzheimer's Disease, CAPNS1 is significantly upregulated in post-mortem AD brain tissue compared to age-matched controls (Chaparral AD proteomics; mean log2 fold-change = +0.67). This elevation is consistent with the role of calpains in proteolytic cascades activated during neurodegeneration and may reflect increased calcium dysregulation and cytoskeletal breakdown characteristic of AD pathology.