Exosomal lactate dehydrogenase A and histone lactylation: Redefining the metabolic language of cytopathology

Once regarded merely as a metabolic byproduct of anaerobic glycolysis, lactate has now been recognized as a signaling metabolite capable of influencing gene expression through histone lactylation.However, the discovery of histone lactylation by Zhang et al. redefined lactate as an active participant in gene regulation. [1]Lactate is no longer metabolic debris; it is a signaling metabolite that can inscribe epigenetic marks on chromatin, directly shaping transcriptional programs.At the heart of this transformation lies lactate dehydrogenase A (LDHA), a pivotal enzyme connecting energy flux with transcriptional control.Emerging evidence that LDHA can travel through exosomes further extends this paradigm beyond individual cells. [2,3]It suggests that metabolism itself can be communicated and that metabolic state is not confined to cytoplasm but broadcast through extracellular vesicles.This revelation compels cytopathologists to rethink what they see under the microscope: Not static morphology, but living traces of metabolic dialog.