β-Klotho–fibroblast growth factor receptor 1c complex (β-Klotho/FGFR1c complex)

The β-Klotho–fibroblast growth factor receptor 1c (β-Klotho/FGFR1c) complex is a membrane-bound heterodimeric receptor system that serves as the primary signaling complex for endocrine fibroblast growth factors, notably FGF21 and FGF19[1][2][3][6]. β-Klotho is a single-pass transmembrane protein with two glycosidase-like domains (KL1, KL2), acting as a high-affinity co-receptor that confers endocrine FGF specificity to FGFR1c, a tyrosine kinase receptor isoform[1][5][9]. Ligand binding (e.g., FGF21) simultaneously engages both β-Klotho and FGFR1c, stabilizing the active signaling complex and initiating intracellular pathways that regulate metabolic processes such as glucose and lipid homeostasis[1][2][4]. The β-Klotho/FGFR1c complex is highly expressed in metabolic tissues like liver and adipose, and is a validated therapeutic target for metabolic disorders, with multiple investigational drugs and biologics in development that either mimic or modulate its activity[6][7].

Other names

βKlotho–FGFR1c complexKLB–FGFR1cFGFR1c/β-Klotho receptor complexFGF21 receptor (when referring to the specific heterodimeric complex)

Agonist binding to β-Klotho/FGFR1c complex triggers receptor dimerization and activation of FGFR1c's tyrosine kinase activity, initiating downstream signaling. Primary pathways: RAS–MAPK and PI3K–AKT signaling cascades.