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Transmembrane protein 16A (Anoctamin-1), commonly known as **TMEM16A** or **ANO1**, is a calcium-activated chloride channel that forms a homodimeric membrane protein with each subunit independently conducting chloride ions[2][3][4][6]. This channel is activated by increases in intracellular Ca²⁺ concentration, coupling chloride ion conduction to various physiological processes, including epithelial secretion, smooth muscle contraction, and control of neuronal excitability[3][4][6]. TMEM16A is widely expressed in epithelial, neuronal, and smooth muscle tissues and is implicated in diseases such as asthma, cystic fibrosis, hypertension, and multiple cancers—where it is also used as the immunohistochemical marker DOG1 for diagnosing gastrointestinal stromal tumors[4][6]. Pharmacological modulation of TMEM16A is being explored for therapeutic benefits in disorders of fluid secretion and airway hyperresponsiveness, though safety challenges remain due to the channel’s role in multiple organ systems and the structural similarity to other TMEM16 family members[6].
Open-channel blockade (e.g., by 1PBC): direct pore occlusion; Negative allosteric modulation or inhibition of channel gating (e.g., NPPB, niflumic acid, T16Ainh-A01); Attenuation of Ca²⁺-induced channel activation
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