{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPIEZO2 is a mechanically activated non‐selective cation channel that serves as a principal transducer of diverse mechanical forces in specialized sensory cells. It is robustly expressed in proprioceptive neurons—with sensory endings innervating muscle spindles and Golgi tendon organs—and in low‐threshold mechanoreceptors of the skin, such as Merkel cells, Meissner corpuscles, and other touch‐sensitive afferents. These channels are essential for delicate discrimination of light touch, vibration, and proprioception, and their functional diversity is enhanced by extensive alternative splicing, which tunes properties such as calcium sensitivity and inactivation kinetics."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMutations in PIEZO2 have been directly linked to a spectrum of developmental disorders characterized by impaired mechanotransduction. Variations—whether by gain‐ or loss‐of‐function mutations—disrupt proper proprioceptive feedback and tactile sensation, leading to congenital joint contractures, craniofacial dysmorphisms, and conditions such as distal arthrogryposis, Gordon syndrome, and Marden–Walker syndrome."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "21"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nPIEZO2 activity is finely regulated by various biochemical modulators, which in turn can alter its current amplitudes, gating kinetics, and force sensitivity. Inflammatory mediators such as bradykinin and cellular signaling pathways including those mediated by protein kinase A have been shown to sensitize PIEZO2, thereby contributing to mechanical hyperalgesia under inflammatory conditions. In addition, interactions with other proteins like TMC7 can inhibit PIEZO2 current, underscoring a complex regulatory network that holds promise for therapeutic intervention targeting mechanically evoked pain."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "22", "end_ref": "29"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its canonical role in cutaneous and proprioceptive mechanotransduction, PIEZO2 functions across a broad range of physiological contexts. It contributes to visceral mechanosensation by mediating low‐threshold detection of bladder stretch and orchestrating micturition reflexes, while in the gastrointestinal tract, it regulates serotonin release from enterochromaffin cells. PIEZO2 also influences cellular and tissue mechanics in the context of tumor progression, exhibits roles in ocular physiology and aqueous humor dynamics, and even participates in sexual arousal by transducing subtle perineal touch. Moreover, its expression in dental tissues, certain enteric neurons, cardiac cells, and discrete regions of the brain highlights its widespread involvement in translating mechanical stimuli into appropriate cellular responses."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "30", "end_ref": "45"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Seung-Hyun Woo, Viktor Lukacs, Joriene C de Nooij, et al. 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