Calpain 14

Calpains are a family of intracellular, calcium-dependent cysteine proteases that are involved in a variety of regulatory processes, including cytoskeletal dynamics, cell cycle progression, signal transduction, gene expression and apoptosis.

Calpanins are associated with a number of disease processes, in particular eosinophilic tissue inflammation such as eosinophilic esophagitis (EoE), which is triggered by allergic hypersensitivity to food and is associated with genetic variants of calpain 14 (CAPN14).

Structurally, CAPN14 has classical calpain motifs, including a cysteine protease core. Compared to other human calpains, CAPN14 has a unique expression pattern, with the highest levels in the upper gastrointestinal tract, particularly in the squamous epithelium of the esophagus.

The gene encoding this cysteine protease, the CAPN14 gene, is located on chromosome 2p23.1-p21 and is most homologous to CAPN13 (36% sequence identity), which is located 365 kb downstream of CAPN14. CAPN14 is located in an epigenetic hotspot regulated by IL-13, a TH2 cytokine that is increased in EoE patients and has been shown to be a mediator of the disease. Diw cysteine protease CAPN14 has disruptive effects on the esophageal epithelium by impairing epithelial barrier function in association with loss of desmoglein-1 expression, and plays a regulatory role in the repair of epithelial alterations induced by IL-13. CAPN14 is thus a unique protease with distinct tissue-specific expression and function in patients with EoE and represents a potential therapeutic target for EoE and related eosinophilic and allergic diseases.

1. Litosh VA et al. (2017) Calpain-14 and its association with eosinophilic esophagitis. J Allergy Clin Immunol 139:1762-1771.