Yeast mutants defective in sphingolipid mannosylation accumulate inositol phosphorylceramide C (IPC-Cor Na ؉ tolerance. Instead, we find that Hor7p-overproducing cells display an increased resistance to high salt, sensitivity to low pH, and a reduced uptake of methylammonium, an indicator of the plasma membrane potential. These phenotypes are induced through a mechanism independent of the plasma membrane H ؉ -ATPase, Pma1p. Our findings suggest that induction of Hor7p causes a depolarization of the plasma membrane that may counteract a Ca 2؉ -induced influx of toxic cations in IPC-C-overaccumulating cells.