GSK-3 role in autophagy regulation has been studied in the past few years.Therefore, sequential phosphorylation of TSC2 by AMPK and GSK-3 occurs and these events may lead to mTOR pathway inhibition [67].Inoki and colleagues have also shown that GSK-3 inhibits mTOR pathway by phosphorylating the tumor suppressor TSC2 in an AMPK-priming phosphorylation-dependent manner.It has been clarified that GSK-3 regulates mTORC1 by phosphorylating the mTOR-associated scaffold protein raptor (regulatory-associated protein of mTOR) on Serine 859.GSK-3 inhibition reduces mTOR and raptor interaction leading to reduced phosphorylation of both p70S6K1 and ULK-1 and to increased autophagic flux [64].This occurs through GSK-3 dependent regulation of the transcription factor EB (TFEB), that is, a master regulator of autophagy and lysosomal biogenesis [65].or GSK-3?