GNG5 (G protein subunit gamma 5) is a critical component of heterotrimeric G-protein complexes that functions in multiple cellular signaling pathways and disease processes 1. As part of the G-protein machinery, GNG5 forms dimers with G-beta subunits and is essential for GTPase activity, GDP-GTP exchange, and G protein-effector interactions 1. The protein plays diverse roles across different biological contexts. In Alzheimer's disease, GNG5 expression is upregulated in hippocampal-entorhinal regions and promotes Aβ42 production by directly interacting with presenilin 1 (PS1), the catalytic subunit of γ-secretase, thereby regulating cleavage preference toward pathogenic Aβ42 2. GNG5 also enhances Rab5 activation, increasing early endosome numbers where Aβ42 is primarily produced 2. In cortical development, GNG5 controls the number of apical and basal progenitors and regulates neuronal migration, with dysregulation contributing to cortical malformations like periventricular heterotopia 3. Clinically, GNG5 serves as a prognostic biomarker in multiple cancers, including gliomas and hepatocellular carcinoma, where overexpression correlates with poor survival outcomes 45. In inflammatory conditions like ulcerative colitis, GNG5 expression is downregulated, suggesting protective roles in intestinal inflammation 6.