Increasing evidence implicates Ca(2+)in the control of cell migration. However, the underlying mechanisms are incompletely understood. Acidic Ca(2+)stores are fast emerging as signaling centers. But how Ca(2+)is taken up by these organelles in metazoans and the physiological relevance for migration is unclear. Here, we identify a vertebrate Ca(2+)/H(+)exchanger (CAX) as part of a widespread family of homologues in animals. CAX is expressed in neural crest cells and required for their migration in vivo. It localizes to acidic organelles, tempers evoked Ca(2+)signals, and regulates cell-matrix adhesion during migration. Our data provide new molecular insight into how Ca(2+)is handled by acidic organelles and link this to migration, thereby underscoring the role of noncanonical Ca(2+)stores in the control of Ca(2+)-dependent function.