DEPTOR (DEP domain containing MTOR interacting protein) is a negative regulator of both mTORC1 and mTORC2 complexes that inhibits mTOR kinase activity, thereby controlling cellular growth, metabolism, and autophagy 1. As a natural mTOR inhibitor, DEPTOR participates in several molecular pathways including cell growth, apoptosis, autophagy, and ER stress response, playing a crucial role in maintaining cellular homeostasis 1. The protein's regulation is complex, involving transcriptional and post-transcriptional mechanisms, with its stability maintained through RNA-binding proteins like PUM1 that prevent DEPTOR mRNA degradation 2. DEPTOR exhibits dual roles in cancer, functioning as either an oncogene or tumor suppressor depending on cellular context 3. Decreased DEPTOR expression has been associated with increased susceptibility to idiopathic pulmonary fibrosis, supporting the importance of mTOR signaling in lung fibrosis 4. The UBE2C/CDH1/DEPTOR axis regulates cell cycle progression, where DEPTOR degradation leads to mTORC activation 5. In gastric cancer, DEPTOR upregulation can activate PI3K-Akt signaling and promote glycolysis through mTORC1 feedback inhibition 2. Given its complex regulatory mechanisms and context-dependent functions, DEPTOR represents an important therapeutic target for various diseases including cancer.