H-K-ATPase type 2: relevance for renal physiology and beyond.

H-K-ATPase type 2 (HKA2), also known as the "nongastric" or "colonic" H-K-ATPase, is broadly expressed, and its presence in the kidney has puzzled experts in the field of renal ion transport systems for many years. One of the most important and robust characteristics of this transporter is that it is strongly stimulated after dietary K(+) restriction. This result prompted many investigators to propose that it should play a role in allowing the kidney to efficiently retain K(+) under K(+) depletion. However, the apparent absence of a clear renal phenotype in HKA2-null mice has led to the idea that this transporter is an epiphenomenon. This review summarizes past and recent findings regarding the functional, structural and physiological characteristics of H-K-ATPase type 2. The findings discussed in this review suggest that, as in the famous story, the ugly duckling of the X-K-ATPase family is actually a swan.