Calpain-2 catalytic subunit

Calpain-2 (CAPN2) is a calcium-regulated cysteine protease that catalyzes limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction (UniProt: P17655). It cleaves MYOC at specific sites and proteolytically processes CPEB3 following neuronal stimulation, thereby relieving CPEB3-mediated translational repression to enable synthesis of target mRNAs.

The protein is widely expressed across tissues and participates in calcium-dependent signaling cascades. UniProt records no primary disease associations for CAPN2, though calpain dysregulation has been implicated in neurodegeneration more broadly.

In Alzheimer's disease, Calpain-2 shows elevated abundance in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of +0.539 (Chaparral AD proteomics). This upregulation was detected via TMT-labeled proteomics across four subcellular fractions from a single fraction comparison. The direction and magnitude of this change suggest increased calpain activity may contribute to proteolytic dysfunction in the AD brain.