GNB4 encodes guanine nucleotide-binding protein subunit beta 4, a component of heterotrimeric G protein complexes essential for G protein-mediated signal transduction 1. As part of the Gβγ dimer, GNB4 is required for GTPase activity, GDP-GTP exchange, and G protein-effector interactions in transmembrane signaling pathways. GNB4 is associated with Charcot-Marie-Tooth disease intermediate form (DI-CMT), an autosomal dominant peripheral neuropathy 2. Beyond neuropathy, GNB4 has emerged as a cancer-associated gene; its expression is significantly upregulated in gastric cancer and correlates with aggressive clinical characteristics and poor prognosis 34. H. pylori infection promotes GNB4 upregulation through demethylation of its promoter region via the NF-κB-TET1 pathway, subsequently activating the oncogenic Hippo-YAP1 signaling axis 3. Additionally, a GNB4-derived circular RNA (circ-GNB4) contributes to diabetic nephropathy through the circ-GNB4/miR-23c/EGR1 pathway, regulating mesangial cell proliferation, inflammation, and oxidative stress 5. Recent genetic analyses implicate GNB4 as a candidate gene in atrial fibrillation susceptibility 6. These findings position GNB4 at the intersection of signal transduction, peripheral neuropathy, cancer biology, and metabolic disease pathogenesis.