As an evolutionarily conserved, lysosomal-driven catabolic response to malnutrition, autophagy is inhibited by trophic factors (the TSC-Ras homolog enriched in brain/RHEB pathway) or amino acid supply (the phosphoinositide 3-kinase/PI3K-RHEB pathway) that activate mTOR. Here, RHEB is linked to nutritional deficiency disease.