Fibroblast growth factor 23 and Klotho: physiology and pathophysiology of an endocrine network of mineral metabolism

Annu Rev Physiol. 2013;75:503-33. doi: 10.1146/annurev-physiol-030212-183727.


The metabolically active and perpetually remodeling calcium phosphate-based endoskeleton in terrestrial vertebrates sets the demands on whole-organism calcium and phosphate homeostasis that involves multiple organs in terms of mineral flux and endocrine cross talk. The fibroblast growth factor (FGF)-Klotho endocrine networks epitomize the complexity of systems biology, and specifically, the FGF23-αKlotho axis highlights the concept of the skeleton holding the master switch of homeostasis rather than a passive target organ as hitherto conceived. Other than serving as a coreceptor for FGF23, αKlotho circulates as an endocrine substance with a multitude of effects. This review covers recent data on the physiological regulation and function of the complex FGF23-αKlotho network. Chronic kidney disease is a common pathophysiological state in which FGF23-αKlotho, a multiorgan endocrine network, is deranged in a self-amplifying vortex resulting in organ dysfunction of the utmost severity that contributes to its morbidity and mortality.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Bone and Bones / physiology
  • Endocrine System / physiology*
  • Fibroblast Growth Factors / physiology*
  • Glucuronidase / physiology*
  • Homeostasis / physiology
  • Humans
  • Intestines / physiology
  • Kidney / physiology
  • Minerals / metabolism*


  • Minerals
  • Fibroblast Growth Factors
  • fibroblast growth factor 23
  • Glucuronidase
  • klotho protein