GNG12 is a G protein subunit gamma that functions as a modulator in heterotrimeric G-protein signaling complexes, facilitating G protein-coupled receptor signaling and signal transduction at the plasma membrane. As a component of the G-protein beta-gamma dimer, GNG12 is required for GTPase activity and G protein-effector interactions 1. Mechanistically, GNG12 regulates cellular processes through NF-κB pathway activation. In pancreatic ductal adenocarcinoma, GNG12 promotes cancer cell growth by activating NF-κB signaling, which subsequently upregulates PD-L1 expression and suppresses anti-tumor immunity 2. Similarly, in gliomas, GNG12 overexpression promotes malignant progression through cell adhesion molecule signaling and the AKT/GSK-3β/β-catenin pathway 34. GNG12 exhibits significant disease relevance across multiple cancer types. Elevated GNG12 expression correlates with poor prognosis in gliomas, pancreatic cancer, and promotes immune evasion through PD-L1-mediated checkpoint activation 12. Conversely, low GNG12 expression in osteosarcoma predicts adverse outcomes and reduced adaptive immunity 5. Additionally, GNG12 hypermethylation associates with tuberculosis development and reduced survival outcomes 6. Clinically, GNG12 serves as a prognostic biomarker with diagnostic potential. The protein predicts glioma stability and osteosarcoma survival with high accuracy (ROC AUC 0.920), suggesting utility in patient stratification and therapeutic targeting 35. GNG12 manipulation represents a potential immunotherapy target, warranting further investigation as a novel intervention strategy.