{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Recent studies have established that anoctamin 1 (ANO1/TMEM16A) is a Ca²⁺-activated chloride channel with a broad range of functions in both normal physiology and disease. In secretory epithelia—including those of the salivary glands, airways, and gastrointestinal tract—ANO1 mediates receptor‐activated chloride currents that are essential for fluid secretion and the maintenance of airway surface liquid, thereby contributing to mucociliary clearance and proper glandular function."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the gastrointestinal system, ANO1 is highly expressed in interstitial cells of Cajal—the pacemaker cells that generate slow-wave activity—thus regulating smooth muscle contractility and coordinated motility."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In sensory neurons, ANO1 also acts as a heat sensor responding to temperatures above 44 °C, thereby contributing to nociceptive signaling and pain perception, a role that complements the actions of other thermosensitive channels such as TRPV1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its physiological roles, ANO1 has emerged as an important player in tumorigenesis. Its overexpression and gene amplification in various cancers—including breast and head and neck carcinomas—correlate with enhanced oncogenic signaling (involving pathways such as EGFR, CAMKII, ERK, and cyclin D1), increased cell migration, and altered volume regulation, which collectively contribute to tumor progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n The channel’s activity is tightly regulated by intracellular Ca²⁺, voltage, calmodulin, and alternative splicing events, which together fine-tune its Ca²⁺ sensitivity and gating properties."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Moreover, small-molecule inhibitors that target ANO1 have been identified and show promise in modulating its transient versus sustained currents in a tissue-specific manner, highlighting potential therapeutic applications for conditions such as cystic fibrosis, asthma, pain, and certain cancers."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Overall, these findings underscore ANO1’s critical role as a multifunctional Ca²⁺-activated chloride channel that coordinates epithelial fluid transport, gastrointestinal pacemaking, nociception, and tumorigenic processes.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Young Duk Yang, Hawon Cho, Jae Yeon Koo, et al. 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