Proton concentrations are major determinants of cell function, in part because the properties of many biological molecules are pH dependent, but also because protons are directly involved in cellular processes. us, many proteins have pH-dependent conformations, leading to pH-dependent enzyme activities, and indeed the pH at which a protein is most stable correlates with the pH of its subcellular location (Chan and Warwicker 2009). Moreover, cellular processes such as metabolism and transport are necessarily pH dependent if they require protons or hydroxide ions as substrates. It follows that uncontrolled variations in pH might be disruptive, implying the need to regulate intracellular pH values for optimal cell function. e set point for regulation is likely to vary between subcellular compartments; indeed, dierences in pH across membranes play a crucial role in both bioenergetics and nutrient uptake, and the preferred value for a specic compartment may also vary according to the physiological state of the tissue. Moreover, the nite capacity of the regulation system and/or its response time may permit transient changes in pH that can then be perceived as signals by the perturbed cell.