PFKM (phosphofructokinase, muscle) catalyzes the phosphorylation of fructose-6-phosphate to fructose-1,6-bisphosphate, representing the first committed step of glycolysis 1. As the muscle isoform of phosphofructokinase-1, PFKM is a rate-limiting enzyme in glucose metabolism 2. PFKM expression is transcriptionally regulated by metabolic and oncogenic pathways. The transcription factor ZEB1 directly activates PFKM transcription through a non-classic binding sequence in its promoter, enhancing glycolytic flux and promoting the Warburg effect in hepatocellular carcinoma 2. PFKM mRNA stability is regulated by the m6A reader protein YTHDC1 in an m6A-methylation-dependent manner 3. Additionally, the pre-mRNA splicing factor LUC7L2 regulates PFKM splicing to modulate glycolytic pathway activity 4. Clinically, PFKM deficiency causes glycogen storage disease VII, characterized by muscle weakness from impaired energy metabolism during exercise 1. PFKM activity is dynamically regulated during viral infection: ARRDC4-mediated activation of PFKM increases fructose-1,6-bisphosphate production, enhancing antiviral innate immunity 5. Genetic variants in PFKM are associated with cryptorchidism susceptibility 6. PFKM is selectively activated by glycolytic modulators in contrast to the structurally similar PFKL isoform expressed in immune cells 7.