PFKM, short for Phosphofructokinase, Muscle, encodes a rate-limiting enzyme in the glycolysis pathway. Glycolysis is a crucial metabolic process for energy production and is involved in various biological functions, including cell proliferation, survival, and differentiation [1-6, 9, 10].

In hepatocellular carcinoma (HCC), ZEB1 transcriptionally upregulates PFKM expression, and this ZEB1-PFKM axis is crucial for HCC carcinogenesis and metastasis. Silencing ZEB1 impairs PFKM expression, glycolysis, proliferation, and invasion in HCC cells, and these impairments can be rescued by exogenous PFKM expression [1].

In renal fibrosis, bone marrow mesenchymal stem cell-derived exosomal miR-21a-5p alleviates the condition by repressing PFKM expression and attenuating glycolysis [2].

In osteosarcoma, NAT10-mediated ac4C acetylation affects m6A modification of PFKM mRNA via YTHDC1, regulating glycolysis [3].

In doxorubicin-induced cardiotoxicity, overexpression of PFKM inhibits cell apoptosis and promotes glycolysis and oxidative phosphorylation, while silencing PFKM has the opposite effects [4].

In sepsis, rTM treatment downregulates PFKM expression in macrophages, protecting mice from sepsis [5].

In ovarian cancer cells, S-nitrosylation of PFKM at Cys351 by NOS1 stabilizes its tetramer, contributing to metabolic reprogramming [6].

In summary, PFKM is essential for glycolysis regulation. Studies using gene-manipulation models, such as knockdown in cell lines, have revealed its significant roles in multiple disease conditions, including cancer, renal fibrosis, cardiotoxicity, and sepsis. Understanding PFKM's function provides potential therapeutic targets for these diseases.