Cryo-EM structures of human TMEM120A and TMEM120B

Pain is a protective signal of impending danger, which is essential for our interaction with the environment 1 . The identification of related mechanosensing ion channel (MSC) is fundamentally important for understanding the mechanism of mechanical pain sensing and analgesic drug discovery. A recent study identified TMEM120A, also named TACAN, as an MSC that contributes to mechanosensitive currents in nociceptors 2 . TMEM120A shares no sequence homology with any reported MSCs or other channels. Despite sequence similarity, no mechanically evoked current was detected for heterologously expressed TMEM120B, a homolog of TMEM120A 2 . TMEM120A/B were originally identified as nuclear membrane localized protein that plays an important role in adipocyte differentiation 3 , 4 . A recent study shows that adipocyte-specific knockout of TMEM120A leads to latent lipodystrophy 5 . The molecular basis underlying the physiological functions of TMEM120A is elusive.