Fig.2 LKB1 and AMPK Signaling allows metabolic programming in T cells: Concerning with low nutrient and energy status, the energy stress pathway kinases LKB1 and AMPK are triggered through TCR and CD28 co-stimulatory signals, with AMPK activity mainly triggered by most understood Ca2+-CAMMK2 (calcium calmodulin kinase kinase 2) pathway. Bioenergetic fluctuations in cells such as deprivation of glucose or glutamine or elevation of AMP/ADP-to-ATP ratio, can also activate LKB1–AMPK signaling. The LKB1 cellular localization and post-translational modifications play an important role in its activity. The role of many upstream regulators of LKB1 signaling in T cells metabolic programming is still undiscovered. The activation of LKB1 promote mitochondrial fitness and increased mevalonate metabolism in Treg cells. The downstream kinase AMPK is the best-known kinase of LKB1. LKB1 is a critical metabolic regulator that regulates energy homeostasis in Tregs. AMPK also promotes mitochondrial fitness by increasing mitochondrial mass. Figure created with Biorender.com