The transmembrane protein 206 abbreviated as TMEM206 is an evolutionarily conserved chloride channel that underlies the ubiquitously expressed, proton-activated, outwardly rectifying anion currents. In a new report now published on Science Advances, Zengqin Deng and a multidisciplinary research team at the Washington University School of Medicine, in Saint Louis, U.S. described the cryo-electron microscopy (cryo-EM) structure of the pufferfish TMEM206. The structure formed a trimeric channel with two transmembrane segments and a large extracellular domain. According to the results, Deng et al. showed how an ample vestibule in the extracellular region could be accessed laterally from three side portals, where the central pore contained multiple constructions. For instance, a conserved lysine residue close to the cytoplasmic region of the inner helix, presumably formed the chloride ion selectivity filter. The core structure and assembly resembled those of sodium channels that are unrelated in amino acid sequence, and therefore conduct cations instead of anions. Together with electrophysiology they provided insights on ion conduction and gating for a new class of chloride channels that are architecturally distinct from previously described chloride channel families.