My research interest concerns how organellar pH is regulated under physiological and pathological conditions. The Na+/H+ exchangers (NHEs) play pivotal roles in intracellular pH and cell volume regulation by their transporter function, exchanging extracellular Na+ for intracellular H+. Originally, the NHEs were identified in the plasma membrane as regulators of cytosolic pH. Recently, I have isolated human cDNAs encoding novel NHE isoforms localizing to organellar membranes that are involved in maintaining organellar pH and ion homeostasis. We will further characterize them by organellar ion flux assay and pH measurement in the presence of different pharmacological inhibitors. In addition to these cell-based techniques, in vitro reconstitution systems in liposomes will be developed for more precise functional analyses. We will also investigate NHE-interacting proteins through biochemical, cell biological, genetic and immunological techniques. To further define biological roles of NHE proteins as well as the interacting proteins, we are going to employ genetic approaches in different model-organism systems.