The recent knowledge of the renal epithelial transport systems has exploded with the identification, cloning, and characterization of a large number of membrane transport proteins. The fundamental aspects of these transporters are beginning to emerge at the molecular level and are summarized in the accompanying contributions in this volume of the Annual Review of Physiology. The aim of my review is to integrate this body of knowledge with the understanding of the clinical disorders of human mineral homeostasis that accompany gain, loss, or dysregulation of function of these transport systems. The specific focus is on the best defined human clinical syndromes in which there are derangements in K(+) and Mg(2+) homeostasis.