RASA4 (RAS p21 protein activator 4) is a calcium-dependent GTPase-activating protein that negatively regulates the Ras-MAPK signaling pathway 1. It functions as a suppressor of RAS activity, thereby inhibiting downstream MAPK pathway activation 2. Additionally, RASA4 serves as an adaptor protein regulating actin dynamics and cell adhesion in response to microbial and inflammatory stimuli 3. In cancer biology, RASA4 acts as a tumor suppressor across multiple malignancies. In cervical cancer, RASA4 suppresses proliferation by inhibiting the HIFα signaling pathway and reducing survivin expression 1. In small cell lung cancer (SCLC), epigenetic silencing of RASA4 through DNA hypermethylation promotes tumor progression by activating the Ras-MAPK pathway and inducing epithelial-mesenchymal transition (EMT) 2. Low RASA4 expression correlates with poor patient survival 2. RASA4 is frequently hypermethylated in juvenile myelomonocytic leukemia, associating with poor prognosis and increased relapse risk 4. In colorectal cancer, the miR-4667-5p-RASA4 axis regulates disease progression and cetuximab resistance 5. RASA4 also suppresses HPV-induced cervical transformation by constraining excessive MAPK activation 6. These findings establish RASA4 as a critical negative regulator of oncogenic Ras signaling with broad therapeutic potential as a biomarker and drug target.