In our study, ablation of both NaPi2a co-transporter and Fgf-23 in the same animal resulted in reduced serum phosphate levels which were accompanied by increased urinary phosphate excretion in Fgf-23−/−/NaPi2a−/− mice, reemphasizing the fact that increased NaPi2a activity in the renal proximal tubular epithelial cells is responsible for the severe hyperphosphatemia in Fgf-23−/− mice. This evidence concerns the gene FGF23 and hyperphosphatemia.