Lactate Signal: Modulator of Cellular Energy Production and Anabolism

ABSTRACT Lactate is no longer viewed simply as a glycolytic end‐product, but as a compartmentalized signaling metabolite that coordinates energy production, carbon redistribution, redox balance, and anabolic commitment. This review discusses lactate as a regulator of the catabolism‐anabolism axis, emphasizing two major patterns of molecular interpretation. First, lactate acts through non‐covalent mechanisms, including transporter‐mediated flux, receptor‐dependent sensing, pH‐linked effects, and direct binding to intracellular proteins. These processes allow lactate‐rich states to rapidly couple metabolic flux to signaling pathways. Second, lactate‐associated metabolic states are translated into the dynamic and reversible change of covalent post‐translational modifications, including histone and non‐histone lactylation. Histone lactylation connects glycolytic metabolism to transcriptional regulation, whereas non‐histone lactylation expands lactate‐dependent control to immune signaling, mitochondrial metabolism, DNA repair, cardiovascular stress, tissue remodeling, and cancer progression. We further discuss how extracellular, cytosolic, mitochondrial‐associated, and nuclear lactate pools provide distinct biochemical contexts in which lactate‐dependent mechanisms can operate. By integrating lactate transport, receptor sensing, protein binding, metabolism, and lactylation, this Review uses compartmental organization as a framework for synthesizing how lactate‐rich states influence metabolic adaptation, stress responses, immune regulation, tissue remodeling, disease progression, and, in selected contexts, anabolic or reparative programs.