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The calcium-activated chloride channel (CLCA) protein family, which includes the human homologs CLCA1 and CLCA2, display distinct tissue distribution patterns. CLCA1 is expressed as a precursor protein that is processed into two cell surface associated subunits and a group of proteins. CLCA1 is upregulated by interleukin-9 and regulates the expression of mucins. CLCA1 may provide a therapeutic target to control mucus overproduction in airway disease patients with cystic fibrosis. CLCA2 expression is downregulated in breast cancer, therefore CLCA2 is thought to act as a tumor suppressor in normal cells. CLCA3 (known as Clca3 in mouse) is a structurally divergent member of the CLCA family that does not function as a channel protein. CLCA4 is a CLCA member that is expressed in human rectal mucosa, CLCA5 shows strong expression in eye and spleen, and CLCA6 is primarily expressed in intestine and stomach.