WDR24 is the catalytic component of the GATOR2 complex, a nutrient-sensing hub that activates mTORC1 signaling in response to amino acid availability 1. GATOR2 forms a large cage-like structure with two-fold symmetry, where WDR24 contributes catalytic WD40 β-propeller domains that interact with amino acid sensors Sestrin2 (leucine sensor) and CASTOR1 (arginine sensor) 123. Mechanistically, WDR24 mediates Lys-6-linked ubiquitination of NPRL2, a GATOR1 component, thereby inactivating GATOR1 and allowing mTORC1 activation when amino acids are abundant 45. In amino acid-depleted conditions, GATOR2 is inhibited by sensor protein binding, which restricts WDR24's dynamic propeller domain, preventing GATOR1 inhibition and suppressing mTORC1 2. Beyond amino acid sensing, WDR24 regulates glucose-dependent mTORC1 activation through AMPK-mediated phosphorylation at S155 5. WDR24 also promotes lysosomal acidification and autophagic flux 6. Disease relevance includes cancer, where dysregulated WDR24-GATOR2 signaling drives hyperactive mTORC1 7, making this axis a therapeutic target for conditions with aberrant mTORC1 activation.