FLCN (folliculin) is a multi-functional GTPase-activating protein that serves as a master regulator of nutrient-responsive signaling. Its primary function is to activate mTORC1 by stimulating GTP hydrolysis of RagC and RagD GTPases, converting them to the GDP-bound state 1. This activation is nutrient-dependent; FLCN's activity is inhibited during starvation and activated when amino acids are present 1. FLCN mediates a substrate-specific mTORC1 pathway that phosphorylates the transcription factor TFEB, a master regulator of lysosomal biogenesis and autophagy, through a unique mechanism distinct from canonical mTORC1 substrates like S6K 12. During amino acid starvation, FLCN activity is inhibited via assembly of the lysosomal folliculin complex, allowing TFEB nuclear translocation and autophagy activation 3. FLCN also regulates glycolysis by directly inhibiting lactate dehydrogenase 1. Mutations in FLCN cause Birt-Hogg-Dubé syndrome, characterized by kidney cysts, renal cell carcinoma, and pulmonary cysts; constitutive TFEB activation drives pathology in this condition 14. Additionally, FLCN participates in autophagy regulation by interacting with GABARAP and coordinates with AMPK in controlling TFEB transcriptional activity 5.