Calcium-activated chloride channels (CaCC) are present in many cell types and mediate physiological functions such as epithelial secretion, sensory signal transduction, and smooth muscle contraction. Subunits of these CaCC’s include the transmembrane proteins TMEM16A and TMEM16B. TMEM16A is expressed in epithelial cells of the kidney and lung, pancreas, and sensory neurons and its mRNA is seen in foregut, airway epithelia, and tracheal smooth muscle; mice lacking TMEM16A fail to survive past ten days and show aerophagia and little weight gain. TMEM16A is also overexpressed or amplified in multiple cancers associated with poor survival such as oral cancers and gastrointestinal stromal tumors, suggesting the development of CaCC modulators may be a viable therapeutic strategy.

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