Calcium-activated chloride channel protein (most often referring to the prototypical TMEM16A protein, also called Anoctamin-1) (TMEM16A (anoctamin-1, ANO1); sometimes CaCC for the channel class)

The **calcium-activated chloride channel protein** most commonly refers to **TMEM16A (anoctamin-1, ANO1)**, a ligand-gated ion channel that conducts chloride ions across cell membranes in response to intracellular calcium. TMEM16A is the prototypical member of the TMEM16/anoctamin family, consisting of 10 transmembrane domains and activated by increases in cytosolic Ca²⁺. These channels are broadly expressed in epithelial, endothelial, smooth muscle, and some neuronal cells. Their principal biological roles include regulation of epithelial fluid secretion, control of smooth muscle contraction, and mediation of sensory perception. TMEM16A is implicated as a therapeutic target in diverse diseases including cystic fibrosis (where it may compensate for CFTR dysfunction), cancer (with overexpression in various tumors), hypertension, fibrosis, and some neurological conditions. Several drugs and small molecule inhibitors—such as CaCCinh-A01, T16Ainh-A01, and Ani9—act on TMEM16A by blocking the ion conduction pore or by promoting protein degradation. The channel is also known as DOG1 in the context of GI stromal tumor diagnostics. Despite its therapeutic potential, the ubiquity of TMEM16A requires careful strategies to avoid unwanted systemic effects, especially when targeting diseases that involve secretory epithelia or smooth muscle[1][2][4][6][7][8].

Other names

Calcium-activated chloride channelCaCCTMEM16AAnoctamin-1ANO1Discovered on gastrointestinal stromal tumors 1 (DOG1)Calcium-dependent chloride channelTMEM16 family proteinChloride channel accessory protein (CLCA)Bestrophin

Inhibition of chloride currents (reducing secretion or excitability); Allosteric modulation of channel (pore and non-pore site binding for inhibitors); Modulation of calcium sensitivity and gating; Indirect action via protein depletion/degradation (some inhibitors)