The Klotho gene family as a regulator of endocrine fibroblast growth factors

Mol Cell Endocrinol. 2009 Feb 5;299(1):72-8. doi: 10.1016/j.mce.2008.10.052. Epub 2008 Nov 21.


The Klotho gene encodes a single-pass transmembrane protein and functions as an aging-suppressor gene, which extends lifespan when overexpressed and accelerates the development of aging-like phenotypes when disrupted in mice. Fibroblast growth factor 23 (FGF23) is a bone-derived hormone that regulates phosphate and vitamin D homeostasis. It has been shown that Klotho-deficient mice and Fgf23 knockout mice exhibit identical phenotypes. This observation led to the identification of Klotho as a cofactor essential for interactions between FGF23 and FGF receptors. In addition to the Klotho-FGF23 axis, recent studies has shown that betaKlotho, a Klotho family protein, also functions as a cofactor required for FGF19 and FGF21 signaling and determines the tissue-specific metabolic activities of FGF19 and FGF21. This review summarizes recent progress in understanding of Klotho and betaKlotho function in the regulation of tissue-specific metabolic activity of the endocrine fibroblast growth factors (FGF19, FGF21, and FGF23).

Publication types

  • Review

MeSH terms

  • Animals
  • Endocrine Glands / metabolism*
  • Fibroblast Growth Factor-23
  • Fibroblast Growth Factors / metabolism*
  • Glucuronidase / genetics
  • Glucuronidase / physiology*
  • Humans
  • Klotho Proteins
  • Models, Biological
  • Multigene Family / physiology
  • Organ Specificity / genetics
  • Phosphates / metabolism
  • Signal Transduction / physiology
  • Vitamin D / metabolism


  • FGF23 protein, human
  • Fgf23 protein, mouse
  • Phosphates
  • Vitamin D
  • Fibroblast Growth Factors
  • Fibroblast Growth Factor-23
  • Glucuronidase
  • Klotho Proteins