Non-Classical Effects of FGF23: Molecular and Clinical Features Martínez Heredia, Luis Canelo-Moreno, Juan Manuel García Fontana, Beatriz Muñoz Torres, Manuel Eduardo FGF23 Klotho Calcineurin pathway This article reviews the role of fibroblast growth factor 23 (FGF23) protein in phosphate metabolism, highlighting its regulation of vitamin D, parathyroid hormone, and bone metabolism. Although it was traditionally thought that phosphate–calcium homeostasis was controlled exclusively by parathyroid hormone (PTH) and calcitriol, pathophysiological studies revealed the influence of FGF23. This protein, expressed mainly in bone, inhibits the renal reabsorption of phosphate and calcitriol formation, mediated by the α-klotho co-receptor. In addition to its role in phosphate metabolism, FGF23 exhibits pleiotropic effects in non-renal systems such as the cardiovascular, immune, and metabolic systems, including the regulation of gene expression and cardiac fibrosis. Although it has been proposed as a biomarker and therapeutic target, the inhibition of FGF23 poses challenges due to its potential side effects. However, the approval of drugs such as burosumab represents a milestone in the treatment of FGF23-related diseases. 2024-07-22T10:35:53Z 2024-07-22T10:35:53Z 2024-04-30 journal article Martínez-Heredia, L.; Canelo-Moreno, J.M.; García-Fontana, B.; Muñoz-Torres, M. Non-Classical Effects of FGF23: Molecular and Clinical Features. Int. J. Mol. Sci. 2024, 25, 4875. [https://doi.org/10.3390/ijms25094875] https://hdl.handle.net/10481/93359 10.3390/ijms25094875 eng http://creativecommons.org/licenses/by/4.0/ open access Atribución 4.0 Internacional MDPI