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0 reviewsLactate, the end product of both anaerobic and aerobic glycolysis in proliferating and growing cells—with thelatter process known as the Warburg effect—is historically considered a mere waste product of cell and tissue metabolism. However, research over the past ten years has unveiled multifaceted functions of lactatethat critically shape and impact cellular biology. Beyond serving as a fuel source, lactate is now known to influence gene expression through histone modification and to function as a signaling molecule that impacts awide range of cellular activities. These properties have been particularly studied in the context of both adaptive and innate immune responses. Here, we review the diverse roles of lactate in the regulation of the immunesystem during homeostasis and disease pathogenesis (including cancer, infection, cardiovascular diseases,and autoimmunity). Furthermore, we describe recently proposed therapeutic interventions for manipulatinglactate metabolism in human diseases.