Proton-activated chloride channel of 351 aas and 2 TMSs near the N- and C-termini. TMEM206 is an evolutionarily conserved chloride channel that underlies ubiquitously expressed, proton-activated, outwardly rectifying, anion currents. Deng et al. 2021 reported the cryo-EM structure of pufferfish TMEM206, which forms a trimeric channel, with 6 TMSs, 2 per subunit, each with a large extracellular domain. An ample vestibule in the extracellular region is accessible laterally from the three side portals. The central pore contains multiple constrictions; a conserved lysine residue near the cytoplasmic end of the inner helix forms the presumed chloride ion selectivity filter. The core structure and assembly closely resemble those of the epithelial sodium channel/degenerin family of sodium channels that seem to be unrelated in amino acid sequence and conduct cations instead of anions. Together with electrophysiology, this structure provides insights into ion conduction and gating for these chloride channels (Deng et al. 2021).