RHOF (ras homolog family member F, filopodia associated) is a small GTPase that functions as a plasma membrane-associated molecular switch, cycling between active GTP-bound and inactive GDP-bound states to regulate actin cytoskeleton organization and filopodia formation. Structurally, RHOF exhibits unique properties among Rho GTPases, adopting a multimeric structure that can switch between conformations depending on nucleotide-bound state, and demonstrates slow GDP dissociation kinetics contrary to initial "fast-cycling" classifications 1. RHOF shows conserved GTPase activity mechanisms with other RAS superfamily proteins but maintains distinct structural characteristics 1. In cancer biology, RHOF is significantly overexpressed in various malignancies including acute myeloid leukemia (AML), hepatocellular carcinoma, and B-cell lymphomas 234. In AML, RHOF promotes cancer progression by activating AKT/β-catenin signaling pathways and enhances chemotherapy resistance 2. In hepatocellular carcinoma, RHOF promotes metastasis by modulating metabolic reprogramming through the Warburg effect via AMPK-RAB3D signaling 3. Clinically, high RHOF expression serves as a diagnostic marker for primary mediastinal large B-cell lymphoma with superior discriminative ability compared to traditional markers 5. High RHOF expression consistently correlates with poor prognosis across multiple cancer types, making it a potential therapeutic target and prognostic biomarker 67.