Deptor is an important protein that belongs to the mTORC1 and mTORC2 complexes, able to interact with mTOR and to inhibit its kinase activity. As a natural mTOR inhibitor, Deptor is involved in several molecular pathways, such as cell growth, apoptosis, autophagy and ER stress response. For this reason, Deptor seems to play an important role in controlling cellular homeostasis. Despite several recent insights characterizing Deptor functions and regulation, its complete role within cells has not yet been completely clarified. Indeed, quite recently, Deptor has been associated with chromatin, and it has been demonstrated having a role in transcriptional regulation, controlling in such way endoplasmatic reticulum activity.

From all these observations it is not surprising that Deptor can behave either as an oncogene or oncosuppressor, depending on the cell- or tissue-contexts. This review highlights recent progresses made in our understanding of the many activities of Deptor, describing its transcriptional and post-transcriptional regulation in different cancer cell types. Moreover, here we discuss the possibility of using compounds able to inhibit Deptor or to disrupt its interaction with mTOR as novel approaches for cancer therapy.