GAPDH has mutually exclusive roles as a glycolytic enzyme and as an RNA-binding protein that represses protein translation. High rates of glycolysis engage GAPDH, leaving the translation of mRNAs, such as IFNG and IL2 mRNA, unconstrained. When the rate of glycolysis is inhibited, a variant of the glycolytic enzyme enolase locates to the nucleus where it inhibits the formation of the Foxp3-E2 splice variant, which is expressed in human iTregs with potent immunosuppressive activities. The glycolytic metabolite PEP promotes Ca²⁺/NFAT signaling and thereby T cell activation. Low glucose levels result in reduced PEP inhibiting NFAT and T cell activation. Strategies to increase PEP levels, such as inhibition of PKM or recombinant expression of PCK1, will restore normal T cell activation in low-glucose conditions. The Krebs cycle intermediate succinate contributes to the stabilization of HIF1α protein in inflammatory macrophages. HIF1α accumulates when the hydroxylases (PHDs) that promote HIF1α degradation are inhibited. Hypoxia and ROS also inhibit PHDs. Depending on the context, HIF1α can promote proinflammatory (IL-1β) or antiinflammatory (PD-L1, miR-210) functions in myeloid cells. Succinate also signals through ligating the cell surface receptor SUCNR1. Cytosolic citrate can also be metabolized to produce important inflammatory mediators such as ROS, NO, and prostaglandins (PGs). Citrate can also be metabolized to itaconic acid, which has important antimicrobial functions.