HK2 and rheumatoid arthritis: Tissue oxygen levels in RA joints can drop to 1-2%, compared to 7-9% in healthy synovium, creating a chronic hypoxic state that triggers activation of hypoxia-inducible factor-1α (HIF-1α) (15), Ultimately upregulating key glycolytic enzymes such as hexokinase 2 (HK2), pyruvate kinase M2 (PKM2), and lactate dehydrogenase A (LDHA) (16).