Pyruvate kinase isozyme M2 (PKM2)

Pyruvate kinase isozyme M2 is a key glycolytic enzyme encoded by the *PKM2* gene. It catalyzes the terminal reaction in glycolysis, converting phosphoenolpyruvate to pyruvate with ATP production. PKM2 uniquely exists as both a highly active tetramer and a low-activity dimer; its dimeric form predominates in proliferating cells and cancer, supporting anabolic metabolism, cell survival, and rapid proliferation, a hallmark of tumor cells known as the Warburg effect. PKM2 has additional non-glycolytic functions, particularly in the nucleus, where it acts as a protein kinase, transcriptional coactivator, and regulator of gene expression linked to oncogenic transformation, immune response, and cell fate decisions. PKM2’s role in metabolism, cancer biology, and cellular regulation makes it a major focus as a therapeutic target, cancer biomarker, and drug discovery candidate.

Other names

Pyruvate kinase muscle isozymePyruvate kinase type KCytosolic thyroid hormone-binding protein (CTHBP)Thyroid hormone-binding protein 1 (THBP1)Opa-interacting protein 3 (OIP3)Tumor M2-PK (in cancer studies)

Inhibition of glycolytic activity (blocking pyruvate formation and ATP production in cancer cells) Promotion of tetrameric (high-activity) form to suppress anabolic metabolism and redirect glucose metabolism Disruption of nuclear functions, kinase activity, or transcriptional modulation (where applicable) Inhibition of tumor-specific metabolic reprogramming (Warburg effect)