GNAZ (G protein subunit alpha Z) is a guanine nucleotide-binding protein that functions as a modulator in transmembrane signaling systems 1. As a heterotrimeric G-protein component, GNAZ lacks a typical pertussis toxin modification site, distinguishing it from other G-protein alpha-subunits 1. In normal physiology, GNAZ is highly expressed in neural tissue and plays a role in inner ear function, potentially maintaining ionic balance of cochlear fluids 1. In pancreatic islets, GNAZ mediates FFAR4-coupled inhibition of somatostatin secretion from delta cells, though species differences exist in its mechanism of action 2. In disease contexts, GNAZ overexpression is a significant oncogenic driver in hepatocellular carcinoma (HCC). High GNAZ expression correlates with poor prognosis, reduced overall survival, and advanced clinicopathological characteristics 3. GNAZ promotes HCC progression through multiple mechanisms: it facilitates G0/G1 cell cycle progression by upregulating cyclin D, cyclin E, and CDK2 3, and promotes vasculogenic mimicry via ERK pathway phosphorylation 4. GNAZ transcription is regulated by the lncRNA CDKN2B-AS1/E2F1 axis 5. Additionally, GNAZ mutations contribute to neurofibromatosis phenotype severity through MAPK pathway activation 6, and preliminary evidence suggests GNAZ polymorphisms may associate with bipolar disorder susceptibility 7.