DGKG encodes diacylglycerol kinase gamma, a lipid kinase that phosphorylates diacylglycerol to generate phosphatidic acid, thereby regulating signaling pathways controlled by these two competing second messengers. The enzyme is particularly enriched in the cerebellum, where it modulates protein kinase C gamma activity and influences dendritic development and motor coordination of Purkinje cells. DGKG displays context-dependent roles across cancer types. In hepatocellular carcinoma, endothelial DGKG is upregulated under hypoxia via HIF-1α activation and promotes tumor angiogenesis and immunosuppressive regulatory T-cell differentiation through the ZEB2/TGF-β1 axis 1. In glioblastoma, a hypoxia-induced alternatively spliced DGKG transcript (DGKG-Δ exon13) enhances proliferation, migration, and invasion more potently than wild-type DGKG 2. Conversely, in colorectal cancer, DGKG promoter hypermethylation silences expression in 51.8% of primary tumors, and ectopic DGKG expression suppresses migration and invasion while inhibiting Rac1 activity, suggesting a tumor suppressor function 3. In oral squamous cell carcinoma, DGKG overexpression correlates with poor prognosis and enhanced cell invasion 4. Genome-wide association studies identify DGKG variants as associated with epilepsy risk 5 and primary open-angle glaucoma 6. Recent evidence suggests dasatinib, a tyrosine kinase inhibitor used in leukemia therapy, may target DGKG in aggressive pituitary neuroendocrine tumors 7. Targeting endothelial DGKG combined with anti-PD-1 and anti-VEGFR-2 blockade enhanced therapeutic efficacy in hepatocellular carcinoma models, positioning DGKG inhibition as a potential precision therapy strategy.