Renal VDR actions. In the proximal tubule cells, CYP27B1 expression is suppressed by 1,25(OH)2D3 and FGF23. FGF23 also stimulates phosphate excretion by decreasing the expression of the phosphate transporters NPT2a/c in the apical membrane. FGF23 may signal by binding to the few FGFR1-Klotho complexes in the proximal tubules or by inducing a paracrine factor (factor X) in the distal tubules where abundant FGFR1-Klotho complexes are present. Renal calcium reabsorption in the distal tubule is stimulated by 1,25(OH)2D3. 1,25(OH)2D3 increases the expression of calbindin-D9k and calbindin-D28k and to a lesser extent of TRPV5. The extrusion of calcium at the basolateral side is mediated by PMCA1b and NCX1. Two models are proposed on how Klotho and FGF23 regulate TRPV5 expression: 1) secreted Klotho (sKlotho) is considered to hydrolyze sugar residues from the glycan chains on TRPV5 resulting in better entrapment of TRPV5 in the apical membrane; and 2) FGF23 binds to the basolateral FGFR1-Klotho complex, which stimulates intracellular transport of TRPV5 to the plasma membrane.