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

Hiroshi Kurosu, Makoto Kuro-o

Research output: Contribution to journalReview articlepeer-review

155 Scopus citations


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 βKlotho, 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 βKlotho function in the regulation of tissue-specific metabolic activity of the endocrine fibroblast growth factors (FGF19, FGF21, and FGF23).

Original languageEnglish (US)
Pages (from-to)72-78
Number of pages7
JournalMolecular and Cellular Endocrinology
Issue number1
StatePublished - Feb 5 2009


  • FGF15
  • FGF19
  • FGF21
  • FGF23
  • Klotho
  • Metabolism
  • βKlotho

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology


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