RRAGD (Ras related GTP binding D) is a guanine nucleotide-binding protein that functions as a critical regulator of mTORC1 signaling in response to amino acid availability. RRAGD forms heterodimeric Rag complexes with RagA or RagB, cycling between inactive (GTP-bound) and active (GDP-bound) conformations 12. In its active GDP-bound state, RRAGD recruits mTORC1 to lysosomes for activation by RHEB, promoting anabolic processes 12. RRAGD also participates in non-canonical mTORC1 signaling independent of RHEB, mediating recruitment of the transcription factors TFEB and TFE3 to regulate lysosomal biogenesis and autophagy 3. This TFEB-dependent pathway operates as a substrate-specific mechanism sensitive to amino acid availability but insensitive to growth factor signaling 3. Beyond nutrient sensing, RRAGD promotes aerobic glycolysis in hepatocellular carcinoma and is upregulated by the oncogene MYC 4. Clinically, RRAGD mutations cause autosomal dominant kidney hypomagnesemia with cardiomyopathy, characterized by renal magnesium and potassium wasting and varying cardiac dysfunction severity 56. These disease-causing variants constitutively activate non-canonical mTORC1 signaling, disrupting TFEB nuclear translocation and lysosomal function 6.