GNG4 (G protein subunit gamma 4) functions as a component of heterotrimeric G-protein complexes involved in G protein-coupled receptor signaling pathways, where it facilitates GTPase activity and effector interactions 1. In cancer contexts, GNG4 demonstrates tissue-specific roles with opposing functions across different malignancies. In glioblastoma, GNG4 acts as a tumor suppressor that is epigenetically silenced through hypermethylation and inhibits SDF1α/CXCR4-dependent chemokine signaling, particularly in mesenchymal subtypes 1. Conversely, GNG4 is overexpressed in lung adenocarcinoma and colon adenocarcinoma, where elevated expression correlates with poor prognosis, enhanced tumor cell proliferation, migration, and immunosuppressive phenotypes 23. In acute myeloid leukemia, GNG4 downregulation is associated with triple-mutated NPM1/FLT3-ITD/DNMT3A cases that have extremely poor survival outcomes 4. GNG4 also shows relevance in neurological contexts, with genetic variations associated with cognitive decline during aging and higher expression in hippocampus and fetal astrocytes 5. Additionally, GNG4 expression is regulated by m6A methylation modifications and may serve as a diagnostic marker for ulcerative colitis 67.