Among the factors that are known to regulate renal inorganic phosphate (Pi) handling, 1,25(OH)2Vitamin D3 is suggested to stimulate proximal tubular phosphate reabsorption. Recently, we investigated the role of 1,25(OH)2Vitamin D3 in the adaptation of the NaPi-IIa phosphate transporter isoform by a low Pi diet, using two mouse models: deficient for the vitamin D receptor or 25- hydroxy vitamin D3-1-a-hydroxylase (1a-OH). Although, we found that neither VDR nor 1a-OH play a central role in the adaptive regulation of NaPi-IIa, we observed that, in the VDR KO animals, the abundance of NaPi-IIc protein was significantly reduced. Thus, we investigated the effect of 1,25(OH)2Vitamin D3 on NaPi-IIc under normal dietary Pi intake. Parathyroidectomized rats received different treatments: parathyroidectomy alone increased NaPi-IIc expression in the renal brush border membrane, application of 1,25(OH)2Vitamin D3 decreased NaPi-IIc protein levels in PTX rats. Acute administration of PTH (1 hr) to PTX rats did not alter NaPi-IIc abundance, in contrast to NaPi-IIa which was downregulated. It remains to be clarified if the Vitamin D effect on NaPi-IIc is a direct effect or involves increased intestinal Pi absorption and subsequent down-regulation of NaPi-IIc.