FGF4 is a fibroblast growth factor that functions as a critical signaling molecule in embryonic development and metabolic homeostasis. During early development, FGF4 works in concert with WNT3A to specify hindgut tissue and, independently, promotes hindgut morphogenesis and intestinal organoid formation from pluripotent stem cells 12. FGF4 also maintains trophoblast stem cell self-renewal in culture 3. Mechanistically, FGF4 signals primarily through FGFR4 to activate distinct downstream pathways depending on tissue context. In hepatocytes, FGF4-FGFR4 signaling activates the AMPK-Caspase 6 axis to enhance fatty acid oxidation and reduce apoptosis 4, while also phosphorylating ERRγ to suppress CYP2E1-mediated oxidative stress 5. In skeletal muscle, FGF4 upregulates GLUT4 surface expression through an AMPKα-dependent, insulin-independent mechanism 6. Hepatically, FGF4 acts as a direct FXR target that paracrinally suppresses bile acid synthesis genes via FGFR4-LRH-1 signaling 7. Clinically, FGF4 shows therapeutic potential in multiple liver pathologies. Loss of hepatic FGF4 exacerbates nonalcoholic fatty liver disease and alcohol-associated liver injury 45, while recombinant FGF4 administration mitigates steatosis and inflammation. In type 2 diabetes, FGF4 demonstrates superior glucose-lowering efficacy compared to FGF21 6. However, in amyotrophic lateral sclerosis, FGF4-mediated astrocyte rescue is limited by TNFα-driven neuroinflammation 8. Mutations in FGF4 are associated with short-rib thoracic dysplasia 22.