This work not only demonstrated that iFGF23 is directly pathogenic, contributing to both progression and cardiomyopathy, but also revealed a novel potential therapeutic role for the breakdown product: Blockade of iFGF23 signaling using its natural proteolytic product, C-FGF23, was shown to effectively alleviate kidney and cardiac pathology and improve function in murine models of high endogenous FGF23. The gene discussed is FGF23; the disease is cardiomyopathy.