Treg cells exert their suppressive function in several different ways. One mechanism is through the LKB1 pathway that activates the mevalonate pathway, which is crucial for Treg functional fitness and stability [85]. This pathway also activates its metabolite geranyl pyrophosphate (GGPP), which phosphorylates STAT-5 via IL-2 signaling and subsequently support Treg function and lineage stability. Activation of mevalonate genes by LKB1 is required for Treg proliferation and, thereby suppressing the interferon-gamma (IFNy) and interleukin-17A (IL-17A) expression, which is independent of the AMPK signaling [85]. Furthermore, LKB1 induced the mevalonate pathway was also found to maintain intracellular cholesterol homeostasis [87, 91]. LKB1 signaling is key for Tregs to maintain their metabolic and immunological balance to curb apoptotic and functional exhaustion, thereby reinforcing homeostatic control of Tregs. Altogether, these preclinical investigations highlighted that LKB1 is a primary regulator of lipid metabolism in Tregs, which play a regulatory role in modulating Tregs suppressive activity and maintaining the phase of immunotolerance (Figure 2).