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The Transmembrane protein 16 (TMEM16) family, also officially known as the Anoctamin family (ANO), consists of ten evolutionarily conserved eukaryotic membrane proteins (TMEM16A–K, ANO1–10). Most notably, TMEM16A (ANO1) and TMEM16B (ANO2) act as **calcium-activated chloride channels** crucial in epithelial secretion, sensory neuron activity, and smooth muscle contraction. Other members, such as TMEM16F, serve as **calcium-dependent phospholipid scramblases** critical for processes such as blood coagulation. Members of this family are structurally characterized by 10 transmembrane domains arranged as homodimers. TMEM16 proteins are widely expressed in the body and are implicated in cancer, neuromuscular disorders, bleeding syndromes, neurodegeneration, and fluid secretion pathologies. They are considered significant therapeutic targets, and both pharmacological inhibitors and genetic manipulation affect diverse physiological and pathological processes[1][2][3][4][5][6][7].
Channel blocking (e.g., TMEM16A/B antagonism inhibits Ca2+-activated Cl− flow and downstream effects) Disruption of phospholipid translocation (for scramblase family members) Downregulation of epithelial secretion (e.g., pilocarpine-induced saliva reduction by siRNA knockdown)
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