While managing serum phosphate levels, it should be realized that development of overt hyperphosphatemia is a late event in CKD, preceded by a chain of adaptive events, including elevated FGF-23, PTH, and low 1,25 dihydroxy-vitamin D levels, which have been independently associated with high CV risks, BMD, and mortality. The gene discussed is FGF23; the disease is hyperphosphatemia.