Calcium-activated chloride channel regulator 4 (CLCA4)

Calcium-activated chloride channel regulator 4 (CLCA4) is a member of the CLCA family, encoded by the CLCA4 gene, and is structurally related to CLCA1 and CLCA2[3][4][7]. CLCA4 primarily acts as a regulator/accessory of epithelial chloride channels, mediating calcium-dependent chloride conductance rather than serving as a classical ion channel itself[1][3][5][6][7]. It is widely expressed in epithelial tissues, particularly the colon, and functions in modulation of electrolyte transport. CLCA4 also possesses a predicted zinc metalloprotease domain at its N-terminus, suggesting additional enzymatic or regulatory activity[3][5][7]. Loss or downregulation of CLCA4 expression is frequently observed in several epithelial cancers, where it acts as a tumor suppressor by inhibiting EMT, cell migration, and invasion—often through suppression of PI3K/AKT signaling[1][2][3][8]. Low levels of CLCA4 are associated with worsened prognosis and increased metastatic risk in colorectal, breast, and bladder carcinomas[1][2][3][8]. CLCA4 thus serves dual roles in physiological ion transport and as a marker/regulator of tumor progression.

Other names

Chloride channel accessory 4CaCC2Calcium-activated chloride channel family member 4Calcium-activated chloride channel protein 2hCLCA4CaCC-2hCaCC-2UNQ562/PRO1124Chloride channel regulator 4CaCCCalcium-activated chloride channel accessory 4

No approved drugs/mechanisms targeting CLCA4 directly are described in the literature to date. Experimental research implicates CLCA4 in modulation of chloride conductance and regulation of tumor cell behavior (via PI3K/AKT, EMT), but drug-target relationships remain uncharacterized[2][3][7][8].