ABSTRACTWe demonstrate here thatSAP155encodes a negative modulator of K+efflux in the yeastSaccharomyces cerevisiae. Overexpression ofSAP155decreases efflux, whereas deletion increases efflux. In contrast, a homolog ofSAP155, calledSAP185, encodes a positive modulator of K+efflux: overexpression ofSAP185increases efflux, whereas deletion decreases efflux. Two other homologs,SAP4andSAP190, are without effect on K+homeostasis. BothSAP155andSAP185require the presence ofSIT4for function, which encodes a PP2A-like phosphatase important for the G1-S transition through the cell cycle. Overexpression of either the outwardly rectifying K+channel, Tok1p, or the putative plasma membrane K+/H+antiporter, Kha1p, increases efflux in both wild-type andsit4Δstrains. However, overexpression of the Na+-K+/H+antiporter, Nha1p, is without effect in asit4Δ strain, suggesting that Sit4p signals to Nha1p. In summary, the combined activities of Sap155p and Sap185p appear to control the function of Nha1p in K+homeostasis via Sit4p.