Calpain-14 (CAPN14)

Calpain-14 (CAPN14) is a calcium-dependent cysteine protease enzyme in the classical calpain family, encoded by the *CAPN14* gene on chromosome 2p23 and most highly expressed in the esophageal epithelium[3][5][1]. CAPN14 is transcriptionally induced by the cytokine IL-13 and is genetically and functionally linked to eosinophilic esophagitis (EoE), a chronic allergic inflammatory disease of the esophagus[3][5][1]. CAPN14 modulates the esophageal epithelial barrier, in part by promoting degradation of desmoglein-1 (DSG1), leading to epithelial disruption and barrier impairment—a key mechanism in EoE pathogenesis[1][3]. Overexpression or dysregulation of CAPN14 results in loss of epithelial integrity and recapitulates features seen in patient biopsies with EoE[1]. CAPN14 activity can be inhibited by classical calpain inhibitors (E-64, MDL-28170, acetyl-calpastatin, PD151746), but development of CAPN14-selective inhibitors is an ongoing therapeutic challenge[1][3]. The tissue specificity and regulatory control of CAPN14 distinguish it from other calpain family members and underlie its role as a potential therapeutic target in EoE and other Th2/IL-13–driven allergic diseases[3][5][1].

Other names

Calpain-14CAPN14CANP14Calcium-activated neutral proteinase 14CANP 14

Inhibition of CAPN14 blocks calcium-dependent proteolysis and preserves epithelial barrier function Reduces IL-13–induced esophageal epithelial changes