RRAS2, a member of the R-Ras subfamily of Ras-like low-molecular-weight GTPases, is ubiquitously expressed and is considered to regulate cell proliferation and differentiation via the RAS/MAPK signaling pathway [2,4]. It plays a role in various biological processes, such as shaping the TCR repertoire by setting the threshold for negative selection in thymus-derived αβ T cells [5].

In disease-related research, conditional knock-in mice overexpressing wild-type human RRAS2 in mammary epithelial cells developed triple-negative breast cancer (TNBC) in a pregnancy-dependent manner, indicating that overexpression of wild-type RRAS2 is a key driver in TNBC [1]. In osteosarcoma, knockdown of RRAS2 using RNA interference reduced cell proliferation and migration by inactivating the MEK/ERK signaling pathway, suggesting its oncogenic role [3]. Also, germline-activating RRAS2 mutations have been found to cause Noonan syndrome. Functional analyses of mutant RRAS2 in zebrafish models showed craniofacial defects and macrocephaly, demonstrating the in-vivo pathogenicity of these mutations [2].

In conclusion, RRAS2 is crucial in regulating cell processes through the RAS/MAPK pathway. Research using mouse and zebrafish models has revealed its significant roles in breast cancer, osteosarcoma, and Noonan syndrome. These models have provided insights into how RRAS2 dysregulation contributes to disease development, offering potential therapeutic targets for these conditions.