RHOB encodes a small GTPase that functions primarily as a negative regulator of tumorigenesis and a mediator of actin cytoskeleton organization. 1 RHOB belongs to the Rho family of GTPases, which are key regulators of the actin cytoskeleton and coordinators of gene transcription and cell adhesion. 2 RhoB expression is rapidly elevated by genotoxic stress, growth factors, and cytokines, and it limits cell proliferation, survival, invasion, and metastasis; targeted deletion increases tumor formation in Ras-mutant mice, confirming its tumor-suppressive role. Mechanistically, RHOB regulates multiple cellular processes including vesicle trafficking, actin dynamics, and cell signaling. 3 During terminal erythropoiesis, RhoB regulates actin reorganization required for nuclear condensation and extrusion. In pancreatic cancer, reduced RhoB expression promotes gemcitabine resistance through the PI3K/Akt pathway-mediated upregulation of ABC transporters, with lower RhoB associated with poor survival. 4 Disease relevance includes cerebral palsy, where RHOB mutations enhance Rho effector binding and disrupt neuronal connectivity through dysregulation of focal adhesion and cytoskeleton pathways. 5 In inflammatory bowel disease, elevated RhoB levels contribute to ulcerative colitis development by inhibiting goblet cell differentiation and epithelial regeneration through Wnt/p38 MAPK pathway modulation. 6 Additionally, RHOB serves as a potential prognostic biomarker for hepatocellular carcinoma. 7