DIRAS2 is a small GTPase that predominantly exists in the GTP-bound form with low intrinsic GTPase activity 1. It functions as a tumor suppressor through multiple signaling pathways. In pancreatic cancer, DIRAS2 suppresses growth and survival of KRAS-mutant cells by inhibiting MAPK-c-Myc signaling, with its ubiquitylation via the UBE2F-CRL5ASB11 axis regulating its stability 2. Conversely, in triple-negative breast cancer, DIRAS2 is downregulated through the eNAMPT/STAT3 axis, promoting cancer stemness and tumor progression 3. DIRAS2 induces autophagic cell death in ovarian cancer by inhibiting AKT1-MTOR and RAS-MAPK pathways while modulating FOXO3 and TFEB nuclear localization 1. Beyond cancer, DIRAS2 is highly expressed in hippocampus and cerebral cortex, with expression in glutamatergic and catecholaminergic neurons, supporting its role as an ADHD candidate gene affecting neurodevelopmental processes 45. DIRAS2 variants also associate with postpartum depression susceptibility 6. These findings establish DIRAS2 as a multifunctional GTPase with context-dependent roles in cancer suppression and neuropsychiatric disease.