LKB1 protein kinase was initially identified in Peutz Jeghers syndrome (PJS),37 and later it has been considered a master serine/threonine kinase involved in diverse physiological processes.38 Accumulating evidence has demonstrated that LKB1 can phosphorylate and activate many AMPK-related kinases on their T-loop (Fig. 1b).18–21 Genetically, deletions of LBK1 are frequently occurred in NSCLCs, especially in KRASG12D-bearing NSCLCs,39,40 indicating that LBK1 is a potent tumor suppressor gene. This evidence concerns the gene PRKAA2 and Peutz-Jeghers syndrome.