TMEM120A

Transmembrane protein 120A (TMEM120A), also known as TACAN or C7orf55, is a mechanosensitive ion channel implicated in cellular mechanotransduction and nociception. Predominantly localized to the plasma membrane with N-terminal palmitoylation sites, it functions as a sensor of mechanical forces, particularly in nociceptive neurons, where it mediates mechanical pain hypersensitivity under inflammatory or neuropathic conditions. TMEM120A interacts with lipid bilayers and modulates membrane tension, though its precise gating mechanism remains debated. It is associated with pathways involving mechanical signal transduction, neuronal hyperexcitability, and inflammatory pain signaling. Dysregulation of TMEM120A has been linked to mechanical allodynia, neuropathic pain syndromes, and potential roles in cardiovascular or musculoskeletal disorders due to its mechanosensory properties. Current research explores TMEM120A as a therapeutic target for chronic pain, with preclinical studies investigating small-molecule inhibitors and monoclonal antibodies to disrupt its channel activity. Structural studies using cryo-EM have advanced understanding of its homodimeric architecture, though pharmacological modulation remains challenging due to overlapping functions with Piezo channels in mechanosensation.

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Recombinant Human Ion channel TACAN (TMEM120A), partial