The K(+) and Na(+) concentrations in living cells are strictly regulated at almost constant concentrations, high for K(+) and low for Na(+). Because these concentrations correspond to influx-efflux steady states, K(+) and Na(+) effluxes and the transporters involved play a central role in the physiology of cells, especially in environments with high Na(+) concentrations where a high Na(+) influx may be the rule. In eukaryotic cells two P-type ATPases are crucial in these homeostatic processes, the Na,K-ATPase of animal cells and the H(+)-ATPase of fungi and plants. In fungi, a third P-type ATPase, the ENA ATPase, was discovered nineteen years ago. Although for many years it was considered to be exclusively a fungal enzyme, it is now known to be present in bryophytes and protozoa. Structurally, the ENA (from exitus natru: exit of sodium) ATPase is very similar to the sarco/endoplasmic reticulum Ca(2+) (SERCA) ATPase, and it probably exchanges Na(+) (or K(+)) for H(+). The same exchange is mediated by Na(+) (or K(+))/H(+) antiporters. However, in eukaryotic cells these antiporters are electroneutral and their function depends on a DeltapH across the plasma membrane. Therefore, the current notion is that the ENA ATPase is necessary at high external pH values, where the antiporters cannot mediate uphill Na(+) efflux. This occurs in some fungal environments and at some points of protozoa parasitic cycles, which makes the ENA ATPase a possible target for controlling fungal and protozoan parasites. Another technological application of the ENA ATPase is the improvement of salt tolerance in flowering plants.