May be involved in mediating calcium-activated chloride conductance. May play critical roles in goblet cell metaplasia, mucus hypersecretion, cystic fibrosis and AHR. May be involved in the regulation of mucus production and/or secretion by goblet cells. Involved in the regulation of tissue inflammation in the innate immune response. May play a role as a tumor suppressor. Induces MUC5AC. The 75 kDa N-terminal and a 35 kDa C-terminal products are fully secreted into extracellular environment as a soluble complex of two glycoproteins. Exclusively expressed in the digestive and respiratory tracts and in the uterus (at protein level). Expressed in small intestine, colon, stomach, and uterus and slightly expressed in trachea tissue. Exclusively expressed in the mucin granule membranes of gastrointestinal, respiratory, and uterine goblet cells and other mucin-producing cells. In the colon, expressed in the surface mucous cells. In the stomach highly expressed in the surface epithelium in the pylorus. Strongly expressed in the airway epithelium of lung tissues associated with airway hyperresponsiveness (AHR). By IL3, IL4 and IL9 in the lung. Increases in the bronchiolar epithelium of asbestos-induced fibrogenesis. Decreases in cystic fibrosis knockout mice. The metalloprotease region is responsible for autoproteolytic processing. It can also cross-cleave other CLCA substrates. The 110 kDa translation product is autoproteolytically cleaved by the metalloprotease domain in the endoplasmic reticulum into a 75 kDa N-terminal and a 35 kDa C-terminal products that remain physically associated with each other. The cleavage is necessary for calcium-activated chloride channel (CaCC) activation activity. Glycosylated. Mice exhibit significantly increased bronchoalveolar lavage (BAL) inflammation consisted predominantly of neutrophils; have decreased goblet cell hyperplasia as well as decreased mucus production; have decreased airway hypersensitivity after cholinergic provocation with methacholine. Belongs to the CLCR family.