Two non-homologous proximal tubular apical Na/Pi-cotransport systems (type I and type II) have been identified thus far by expression cloning. Subsequent studies provided evidence that the type II Na/Pi-cotransporter represents a target for the physiological and pathophysiological regulation of proximal reabsorption of phosphate. The exact role of the type I Na/Pi-cotransporter in proximal Pi-reabsorption and eventually also in the renal handling of other substrates, such as organic anions, is currently less clear and needs further investigation. Evidence was obtained that acute changes of brush border membrane Na/Pi-cotransport involves endo- and exocytic movement of type II Na/Pi-cotransporters. In particular, we elucidated if and how phosphorylation reactions are involved and defined the intracellular structures of the endo/exocytic apparatus involved. At the level of the gene it will be necessary to elucidate its organization in order to understand the mechanisms involved in chronic regulations of Na/Pi-cotransport related to the type II Na/Pi-cotransporter. Furthermore, for structural investigations of these integral membrane proteins, they have to be isolated in sufficient quantities. Thus far the type II cotransporter (NaPi-2) has been expressed in Sf9 insect cells , which may eventually allow a purification of this protein.