FGF23 signaling can take place through several routes: a canonical route where FGF23 binds to the FGF receptor 1c (FGFR1c) at the proximal tubule in the presence of the co-factor Klotho, inducing phosphaturia and suppressing vitamin D activation; a klotho-independent route through another FGF receptor (FGFR4), activating distinct intracellular pathways (calcineurin/NFAT), promoting left ventricular hypertrophy in the heart, and through a noncanonical route involving a circulating, soluble form of Klotho that can also bind to FGF23 receptors [17▪]. This evidence concerns the gene FGFR4 and left ventricular hypertrophy.