RRAS2 is a RAS-related small GTPase that functions as a GTP-binding protein with GTPase activity, primarily regulating the RAS-MAPK signaling pathway to control cellular processes including craniofacial development 1. RRAS2 interacts with phosphoinositide 3-kinase α (PI3Kα) through its RAS-binding domain, with this interaction crucial for PI3K-AKT-mTOR pathway activation 2. In vascular smooth muscle cells, RRAS2 preserves homeostasis by maintaining GTF2I phosphorylation and nuclear translocation to sustain contractile gene expression, preventing pathological phenotypic switching 3. Germline RRAS2 mutations cause Noonan syndrome 12, characterized by facial dysmorphism, short stature, cardiac defects, and developmental delay 1. In cancer, RRAS2 exhibits oncogenic roles through distinct mechanisms: wild-type RRAS2 overexpression drives triple-negative breast cancer in pregnancy-dependent manner, occurring in 68% of breast tumors 4, while specific hotspot mutations (Q72L) activate MAPK and PI3K pathways and represent actionable drivers in ~0.45% of lung cancers 5. RRAS2 mutations also appear as recurrent hotspots across 41 cancer types 6, and RRAS2 serves as a potential biomarker for cetuximab response prediction in colorectal cancer 7. Therapeutic approaches include molecular glues enhancing PI3Kα-RRAS2 binding for insulin-independent glucose uptake in diabetes 8 and pan-RAS inhibitors targeting mutant RRAS2-driven cancers.