First, SphK2 affects HCC development by regulating lipid metabolic balance: SphK2 deficiency downregulates the expression of ceramide transport protein (CERT), significantly decreasing the ratio of pro-cancer sphingomyelin (SM) to anti-cancer ceramide, thereby inhibiting HCC development in NAFLD liver; conversely, overexpression of CERT can reverse this effect and restore hepatocyte proliferation, colony formation, and cell cycle progression (34). This evidence concerns the gene SPHK2 and hepatocellular carcinoma.