CASTOR2 functions as a cytosolic arginine sensor that negatively regulates mTORC1 signaling through the GATOR complex. As part of homodimers or heterodimers with CASTOR1, CASTOR2 directly binds and inhibits GATOR2, thereby suppressing mTORC1 activity 1. Unlike CASTOR1, which responds to low arginine levels, CASTOR2 specifically senses high arginine concentrations and induces conformational changes at its ACT domain that promote dissociation from the GATOR2 component Mios, allowing mTORC1 activation 2. This dual-sensor system enables fine-tuned mTORC1 regulation across different arginine availability ranges. CASTOR2 is highly expressed in muscle tissue and regulates myogenesis in response to arginine availability 2. Clinically, CASTOR2 dysregulation contributes to cancer pathogenesis: KSHV suppresses CASTOR2 expression via viral miRNAs to activate mTORC1 and promote tumorigenesis 3, and CASTOR2 has been identified as a prognostic enhancer RNA marker for non-small cell lung cancer metastasis 4. Additionally, CASTOR2 is a FOXO1 target gene upregulated during fasting-induced muscle atrophy 5, suggesting roles in catabolic regulation.