A few years later, FGFR4 was identified to be the main effector of FGF23 signaling in the heart (78) leading to the conclusion that cardiac hypertrophy induced by FGF23 is mediated by the FGFR4/PLCγ/calcineurin pathway that activate nuclear factor of activated T-cells (NFAT) and consequently pro-hypertrophic NFAT target genes (Figure 2). Here, FGF23 is linked to cardiac hypertrophy.