2 Here, we present the purification and biochemical characterization of the N-terminal domain of subunit 'a', Vph1N, which has been suggested to act as a pH sensor in mammalian cells. 3 Interestingly, our studies demonstrate pH-dependent oligomerization of this domain in vivo and in vitro. Moreover, we identify a membrane proximal region that is required for the pHdependent oligomerization and suggest a speculative model for the regulation of the V-ATPase holo-complex by pH.