Piezo-type mechanosensitive ion channel component 2 (PIEZO2) (PIEZO2)

PIEZO2 is a large, multi-pass transmembrane protein that functions as a mechanically activated, non-selective cation channel (Coste et al., 2010, Science). It is primarily expressed in sensory neurons of the dorsal root ganglia, Merkel cells, and specialized nerve endings, where it serves as the principal transducer of light touch, proprioception, and vibration (Ranade et al., 2014, Nature). Beyond somatosensation, PIEZO2 is critical for internal mechanosensing, including the regulation of lung inflation via the Hering-Breuer reflex and the sensing of bladder fullness (Nonomura et al., 2017, Nature; Marshall et al., 2020, Nature). Mutations in the PIEZO2 gene are associated with several musculoskeletal and sensory disorders, such as distal arthrogryposis type 5 and Gordon syndrome, which involve joint contractures and impaired proprioception (Chesler et al., 2016, NEJM). In the context of drug discovery, PIEZO2 is a major target for treating mechanical allodynia—a condition where normal touch becomes painful—as seen in chronic pain states (Szczot et al., 2018, Sci Transl Med). While specific small-molecule inhibitors are still in early development, research tools like the peptide GsMTx4 demonstrate the potential for modulating this channel to alleviate pain. However, challenges remain regarding selectivity over PIEZO1 and the preservation of essential sensory functions like balance and breathing.

Other names

FAM38BC18orf26Mechanosensitive ion channel Piezo2Protein PIEZO2

Inhibition of mechanically gated cation influx to reduce sensory neuron excitability and pain signaling.