MRAS

MRAS (Muscle RAS oncogene homolog), also known as R-Ras3, is a member of the RAS GTPase superfamily that regulates cell proliferation, differentiation, and survival through GTP-dependent signaling. Functioning as a molecular switch, MRAS activates downstream effectors including RAF-MAPK and PI3K-AKT pathways upon growth factor stimulation. It uniquely interacts with SHOC2-PP1C phosphatase complexes to modulate RAS/MAPK pathway dynamics. Germline mutations in MRAS are linked to Noonan syndrome, characterized by cardiac defects and developmental delays, while somatic mutations drive malignancies such as lung adenocarcinoma and thyroid cancer. Recent studies highlight MRAS overexpression in cardiovascular hypertrophy and atherosclerosis. Though historically considered "undruggable," emerging strategies targeting MRAS include allosteric inhibitors disrupting SHOC2 interactions and PROTAC-based degradation agents, with preclinical candidates showing promise in RAS-addicted cancers.