PFKL, short for phosphofructokinase, liver type, is a key enzyme in glycolysis [2,3,4,5,6,7,8]. It plays a significant role in regulating glucose metabolism and is involved in multiple metabolic pathways. Glycolysis, in which PFKL participates, is crucial for energy production in cells, and abnormal regulation of PFKL can impact overall cellular metabolism and function. Genetic models, such as gene knockout mouse models, have been valuable in studying PFKL's functions.

In tumor cells, glucose deprivation phosphorylates PFKL, reducing its glycolytic activity and enabling it to interact with perilipin 2 (PLIN2). This leads to lipid droplet-mitochondria tethering, enhancing β-oxidation and tumor cell proliferation. Interfering with this cascade inhibits tumor cell growth [1]. In macrophages, phosphorylation of PFKL at Ser775 increases its catalytic activity, promoting glycolysis. In a genetic mouse model where PFKL Ser775 phosphorylation cannot occur, macrophage glycolysis is lower upon activation [4]. In cardiac hypertrophy in male mice, the KLF7/PFKL/ACADL axis modulates cardiac metabolic remodelling, with PFKL being a key target in the regulation of glycolysis and fatty acid oxidation fluxes [5].

In conclusion, PFKL is essential for the integrated regulation of glycolysis, lipid metabolism, and mitochondrial oxidation. Gene knockout mouse models have been instrumental in revealing its role in tumor growth, macrophage-mediated inflammation, and cardiac metabolic remodelling. Understanding PFKL's functions provides insights into disease mechanisms and potential therapeutic targets for related diseases such as cancer and cardiac hypertrophy.