Proton-Activated Chloride Channel: Physiology and Disease.

The maintenance of intracellular and extracellular pH relies on multiple ion transporters/channels. Proton-activated chloride channel (PAC) precisely regulates extracellular and early/late endosomal pH by transporting chloride ion (Cl-) across membranes and has been shown to be implicated in pH imbalance under hypoxic conditions, such as the acidic microenvironments of cancer and ischemia. In this article, the phenotypic characteristics, molecular mechanisms, physiology of PAC and its role in cancer, ischemic stroke and hypoxia will be discussed in order to provide some clues for developing potential therapeutic strategies.