RENAL PATHOPHYSIOLOGY: Edited by Orson W. Moe and Susan E. QuagginFibroblast growth factor receptor as a potential candidate for phosphate sensingTakashi, Yuichia; Fukumoto, SeijibAuthor Information aDepartment of Endocrinology and Diabetes Mellitus, Fukuoka University Chikushi Hospital, Fukuoka bDepartment of Molecular Endocrinology, Fujii Memorial Institute of Medical Sciences, Institute of Advanced Medical Sciences, Tokushima University, Tokushima, Japan Correspondence to Seiji Fukumoto, Department of Molecular Endocrinology, Fujii Memorial Institute of Medical Sciences, Institute of Advanced Medical Sciences, Tokushima University, 3-18-15 Kuramoto-cho, Tokushima, Tokushima 7708503, Japan. Tel: +81 88 634 6440; e-mail: email@example.com Current Opinion in Nephrology and Hypertension: July 2020 - Volume 29 - Issue 4 - p 446-452 doi: 10.1097/MNH.0000000000000618 Buy Metrics Abstract Purpose of review Phosphate plays essential roles in many biological processes. Serum phosphate level needs to be regulated because hypophosphatemia and hyperphosphatemia cause rickets/osteomalacia and ectopic calcification, respectively. Fibroblast growth factor (FGF) 23 is the principal hormone to regulate serum phosphate level. FGF23 is produced by the bone and works to reduce serum phosphate level by binding to FGF receptor (FGFR) 1c and α-Klotho complex in the kidney. It has been unclear how the bone senses the changes of serum phosphate level and how the bone regulates the production of FGF23. Recent findings Our recent results indicate that high extracellular phosphate activates FGFR1c. Its downstream intracellular signalling pathway regulates the expression of GALNT3 encoding a protein involved in the regulation of the posttranslational modification of FGF23 protein. This FGFR1c-GALNT3 axis is considered to be the main regulatory mechanism of enhanced FGF23 production in response to high phosphate. Summary We propose that FGFR1c works as a phosphate-sensing molecule in the regulation of FGF23 production and serum phosphate level. Feedback system is present in the regulation of serum phosphate involving FGFR1c and FGF23. These findings uncover so far unrecognized function of FGFR and molecular basis of phosphate sensing. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.