FGF 23 promotes renal calcium reabsorption through the TRPV 5 channel

α K lotho is thought to activate the epithelial calcium channel T ransient R eceptor P otential V anilloid‐5 ( TRPV 5) in distal renal tubules through its putative glucuronidase/sialidase activity, thereby preventing renal calcium loss. However, α K lotho also functions as the obligatory co‐receptor for fibroblast growth factor‐23 ( FGF 23), a bone‐derived phosphaturic hormone. Here, we show that renal calcium reabsorption and renal membrane abundance of TRPV 5 are reduced in F gf23 knockout mice, similar to what is seen in α K lotho knockout mice. We further demonstrate that α K lotho neither co‐localizes with TRPV 5 nor is regulated by FGF 23. Rather, apical membrane abundance of TRPV 5 in renal distal tubules and thus renal calcium reabsorption are regulated by FGF 23, which binds the FGF receptor‐α K lotho complex and activates a signaling cascade involving ERK 1/2, SGK 1, and WNK 4. Our data thereby identify FGF 23, not α K lotho, as a calcium‐conserving hormone in the kidney.