GNB1 encodes the beta-1 subunit of heterotrimeric G proteins, which function as essential modulators in transmembrane signaling systems by coupling G protein-coupled receptors to intracellular effectors. The GNB1 protein is required for GTPase activity, GDP-GTP exchange, and G protein-effector interactions 1. GNB1 demonstrates diverse cellular functions beyond classical G protein signaling. In hepatocellular carcinoma, GNB1 promotes tumor progression by interacting with BAG2 to activate P38/MAPK signaling pathways, enhancing cell proliferation, migration, and epithelial-to-mesenchymal transition 2. The protein also regulates lipid metabolism in adipocytes, where knockdown reduces lipid droplet accumulation and alters phospholipid profiles 3. Pathogenic variants in GNB1 cause GNB1 encephalopathy, a rare neurodevelopmental disorder characterized by intellectual disability, dystonia, and seizures, with neuronal hyperexcitability resulting from impaired ion channel regulation 4. Notably, GNB1 haploinsufficiency is associated with syndromic obesity and hyperphagia, potentially through interactions with hypothalamic leptin-melanocortin pathways 5. Recent evidence suggests GNB1 variants may contribute to dystonia phenotypes and promote immunosuppressive tumor microenvironments in colorectal cancer liver metastasis 67.