Fibroblast growth factor 21 receptor (FGF21R)

Fibroblast growth factor 21 (FGF21) receptor is a signaling complex primarily composed of fibroblast growth factor receptor 1c (FGFR1c) and the obligate co-receptor beta-Klotho (KLB) [1, 2, 5, 8]. This receptor complex is expressed predominantly in metabolic tissues such as the liver, adipose tissue, and pancreas, where it mediates the endocrine effects of the hormone FGF21 [5, 8, 9]. Activation of the FGF21 receptor pathway enhances insulin sensitivity, promotes fatty acid oxidation, and increases energy expenditure, making it a critical regulator of systemic glucose and lipid homeostasis [4, 8, 15, 23]. In metabolic diseases like nonalcoholic steatohepatitis (NASH/MASH), type 2 diabetes, and obesity, the pathway is often dysregulated, contributing to hepatic steatosis and fibrosis [1, 10, 12, 17]. Therapeutic interventions involve the use of FGF21 analogs or agonistic antibodies that target the FGFR1c/KLB complex to restore or enhance metabolic signaling [4, 12, 18]. Clinical trials have demonstrated that targeting this receptor can significantly reduce liver fat and improve markers of fibrosis [11, 18, 19]. However, safety considerations include gastrointestinal adverse events and potential long-term effects on bone mineral density [10, 11, 19]. Overall, the FGF21 pathway represents a promising therapeutic target for a range of metabolic and inflammatory conditions [1, 12, 21].

Other names

FGF21 pathwayFibroblast growth factor 21 receptor complexFGFR1c-beta-Klotho complexFGF21R

Agonism of the FGFR1c/beta-Klotho receptor complex by FGF21 analogs or bispecific antibodies.