Fgf18, discovered in 1998, is a pleiotropic growth factor. It stimulates major signalling pathways involved in cell proliferation and growth, playing a crucial role in the development and homeostasis of tissues like bone, lung, and the central nervous system. The gene consists of five exons encoding a 207-amino-acid glycosylated protein and is widely expressed in developing and adult chickens, mice, and humans [1].

Knockout studies of Fgf18 in mice lead to perinatal death, with phenotypes such as cleft palate, smaller body size, curved long bones, deformed ribs, and reduced crania, indicating its importance in normal development [1]. In disease-related research, in male mice, Fgf18 deletion in hepatic stellate cells (HSCs) aggravates hepatic ischemia-reperfusion injury (IRI), while Fgf18 treatment alleviates it via the USP16-mediated KEAP1/Nrf2 signaling pathway [2]. In liver fibrosis models, deletion of Fgf18 in hepatocytes attenuates liver fibrosis, and overexpression promotes it by stimulating the proliferation of HSCs [3]. For cardiac hypertrophy, Fgf18 heterozygous and cardiomyocyte-specific Fgf18 knockout male mice exposed to transverse aortic constriction show exacerbated pathological cardiac hypertrophy, while cardiac-specific overexpression alleviates it through the FYN/NOX4 signaling axis [4].

In conclusion, Fgf18 is essential for the development and homeostasis of multiple tissues. Mouse knockout models have revealed its key roles in various biological processes and disease conditions, including development, hepatic IRI, liver fibrosis, and cardiac hypertrophy. Understanding Fgf18 can potentially provide new therapeutic strategies for related diseases.