PKM (pyruvate kinase M1/2) encodes a metabolic enzyme existing as two alternatively spliced isoforms with distinct functions. The M1 isoform, expressed in adult tissues, exhibits constitutive high pyruvate kinase activity independent of allosteric activation 12. In contrast, the M2 isoform predominates in cancer cells and functions as a metabolic switch regulator. PKM2 displays reduced catalytic activity and preferentially translocates to the nucleus where it associates with transcription factors like STAT3 and HIF1α 3. This isoform switch is central to the Warburg effect—the metabolic reprogramming whereby cancer cells favor aerobic glycolysis over oxidative phosphorylation 45. Beyond cancer, PKM2 upregulation contributes to neurodegeneration in Alzheimer's disease, promoting neuronal fate loss and vulnerability through metabolic and transcriptional dysregulation 3. PKM2 also plays roles in osteoarthritis pathogenesis, where its tetrameric form is preserved through PINK1-mediated phosphorylation to maintain mitochondrial homeostasis and prevent cartilage degeneration 6. Therapeutically, PKM isoform switching from M2 back to M1 represents a promising strategy: antisense oligonucleotides successfully inhibited hepatocellular carcinoma growth in preclinical models 4, while LINC01852-mediated suppression of PKM2 splicing restored oxidative phosphorylation and sensitized colorectal cancer cells to chemotherapy 7. PKM thus functions as a critical metabolic node controlling both normal cellular energetics and pathological processes.