Aims: Insulin and insulin-like growth factor IGF1 are known to participate in the regulation of renal tubular calcium and phosphate transport. Insulin and IGF1-dependent signaling involve phosphorylation and thus inactivation of glycogen synthase kinase GSK3. The present study explored, whether PKB/SGK-dependent GSK3 activity participates in the regulation of mineral metabolism. Methods: Dual voltage clamp experiments were performed in Xenopus oocytes expressing the renal phosphate transporter NaPiIIa and electrogenic Na⁺-dependent currents were recorded. Further experiments were performed in mutant mice in which PKB/SGK-dependent GSK3a,b regulation is disrupted by replacement of a serine in the respective SGK/PKB-phosphorylation consensus sequence by alanine (gsk3^KI). These mice were compared to corresponding wild type mice (gsk3^WT) Results: Expression of the mammalian renal phosphate transporter NaPiIIa in Xenopus oocytes was followed by phosphate-induced currents, which were significantly decreased by coexpression of GSK3b. Plasma phosphate concentration was significantly lower and plasma Ca²⁺ concentration tended to be lower in gsk3^KI than in gsk3^WT mice. Despite the lower plasma concentrations, urinary excretion of both, phosphate and Ca²⁺, were significantly higher in gsk3^KI than in gsk3^WT mice. Sodium-dependent phosphate fluxes in isolated brush border membrane vesicles were reduced along with decreased protein expression levels of the Na/phosphate cotransporters NaPi-IIa and NaPi-IIc. The plasma concentrations of both, PTH and 1,25(OH) ₂D₃ were lower in gsk3^KI than in gsk3^WT mice. Similarly, bone density was significantly lower in gsk3^KI than in gsk3^WT mice. Conclusion: The observations identify the GSK3b kinase pathway as a powerful regulator of renal phosphate transport.