The lysosome plays a crucial role in cellular homeostasis by controlling cellular clearance and energy production. The study demonstrates that Transcription Factor EB (TFEB), a master regulator of lysosomal biogenesis, colocalizes with mTOR complex 1 (mTORC1) on the lysosomal membrane. TFEB activity is regulated by mTORC1 phosphorylation, which inhibits its nuclear translocation when nutrients are present. Conversely, pharmacological inhibition of mTORC1, starvation, and lysosomal disruption activate TFEB by promoting its nuclear translocation. The Rag GTPase complex, which senses lysosomal amino acids and activates mTORC1, is essential for the starvation- and stress-induced nuclear translocation of TFEB. These findings indicate that the lysosome senses its content and regulates its own biogenesis through a lysosome-to-nucleus signaling mechanism involving TFEB and mTOR. This mechanism allows the lysosome to adapt its function according to cellular needs.The lysosome plays a crucial role in cellular homeostasis by controlling cellular clearance and energy production. The study demonstrates that Transcription Factor EB (TFEB), a master regulator of lysosomal biogenesis, colocalizes with mTOR complex 1 (mTORC1) on the lysosomal membrane. TFEB activity is regulated by mTORC1 phosphorylation, which inhibits its nuclear translocation when nutrients are present. Conversely, pharmacological inhibition of mTORC1, starvation, and lysosomal disruption activate TFEB by promoting its nuclear translocation. The Rag GTPase complex, which senses lysosomal amino acids and activates mTORC1, is essential for the starvation- and stress-induced nuclear translocation of TFEB. These findings indicate that the lysosome senses its content and regulates its own biogenesis through a lysosome-to-nucleus signaling mechanism involving TFEB and mTOR. This mechanism allows the lysosome to adapt its function according to cellular needs.