GNB2 encodes the β2 subunit (Gβ2) of heterotrimeric G-protein complexes that mediate G-protein-coupled receptor signaling pathways 1. The Gβ2 subunit forms complexes with Gγ subunits and is essential for G-protein function, including GTPase activity and effector interactions. In cardiac tissue, GNB2 regulates G-protein-activated potassium channels (GIRK), with mutations leading to sustained channel activation and membrane hyperpolarization 1. GNB2 also participates in cellular signaling through ERK and Wnt pathways, influencing cell proliferation and migration 2. Disease-associated mutations in GNB2 cause multiple phenotypes: heterozygous missense variants (p.Ala73Thr, p.Gly77Arg, p.Lys89Glu, p.Lys89Thr) result in neurodevelopmental disorders with intellectual disability and dysmorphic features 3, while the p.Arg52Leu variant causes familial sinus node dysfunction and atrioventricular block through enhanced GIRK channel activation 1. Somatic GNB2 mutations are implicated in Sturge-Weber syndrome 4, and polymorphic tandem repeat variations in the GNB2 5'UTR influence heart rate 5. These findings establish GNB2 as critical for normal cardiac conduction, neurodevelopment, and cellular signaling, with mutations causing distinct inherited disorders affecting multiple organ systems.