LDHA (lactate dehydrogenase A) catalyzes the reversible interconversion of pyruvate and lactate with concurrent NAD+/NADH cycling, serving as the final enzyme in anaerobic glycolysis 1. Beyond its canonical metabolic role, LDHA functions as a moonlighting kinase that phosphorylates GPX4 at threonine 95, protecting against ferroptosis in cardiac ischemia-reperfusion injury 2. LDHA drives malignant progression through multiple mechanisms. In pancreatic cancer, LDHA-derived lactate fuels histone lactylation at H3K18, epigenetically activating mitotic checkpoint regulators that create a positive feedback loop amplifying glycolysis 3. In breast cancer, lactate-driven NBS1 lactylation at lysine 388 promotes homologous recombination DNA repair and chemotherapy resistance; genetic or pharmacological LDHA inhibition reverses this resistance 4. LDHA expression correlates with immune evasion: elevated LDHA-derived lactate suppresses T and NK cell function through NFAT inhibition 5, while also inhibiting RLR-mediated antiviral interferon production by directly binding MAVS 6. In glioblastoma, LDHA activates ERK/YAP1/STAT3 signaling to promote macrophage recruitment, establishing tumor-macrophage symbiosis 7. During sepsis, LDHA downregulation impairs neutrophil chemotaxis and phagocytosis via the PI3K/Akt-HIF-1α pathway 8. LDHA inhibition emerges as a therapeutic strategy across cancer and inflammatory contexts, with clinical agents like stiripentol showing promise.