The role of FGF19-FGFR4 signaling pathway in liver health and disease: Guardian or destroyer.

The fibroblast growth factor (FGF) 15/19-FGF receptor (FGFR) 4 signaling pathway is a crucial endocrine regulatory pathway within the FGF family. The FGF15/19-FGFR4 signaling pathway plays multiple key roles in the liver, involving core physiological processes such as metabolic regulation, bile acid homeostasis maintenance, and hepatocyte proliferation and repair, and is also closely related to the pathogenesis of various liver diseases. At present, targeted therapeutic strategies for the FGF19-FGFR4 signaling axis have shown significant therapeutic potential. Agonists that simulate the physiological functions of FGF19 have been proven to effectively regulate bile acid and lipid metabolism in metabolic diseases and improve liver steatosis and fibrosis. Meanwhile, drugs that selectively inhibit FGFR4 have also demonstrated positive anti-tumor activity in specific tumor types driven by FGF19 overexpression. Given the crucial role of FGF19-FGFR4, clarifying the key mechanisms of this pathway in both physiology and pathology, as well as summarizing targeted therapy, is of vital importance. This review highlights the key role of FGF15/19-FGFR4 signaling in regulating liver physiological functions and reveals how its abnormal expression contributes to the occurrence of benign and malignant liver diseases. In addition, this review points out the potential of FGF15/19-FGFR4 signaling as a biomarker in different liver diseases and briefly discusses the existing treatment strategies for this signaling pathway.