GPD2 encodes the mitochondrial glycerol-3-phosphate dehydrogenase 2, a FAD-linked enzyme that serves as the mitochondrial component of the glycerol-3-phosphate shuttle (G3PS) 1. This enzyme catalyzes the oxidation of glycerol-3-phosphate to dihydroxyacetone phosphate in mitochondria, functioning as part of an NADH shuttle system that bridges glucose and lipid metabolism 1. Beyond its traditional bioenergetic role, GPD2 plays critical non-bioenergetic functions in cancer progression by supplying dihydroxyacetone phosphate for ether lipid biosynthesis, which activates the Akt/mTORC1 pathway to promote tumor growth 2. In hepatocellular carcinoma, GPD2 regulates mitochondrial respiration and controls cell migration and invasion through interaction with SPARC protein 3. The enzyme also maintains cancer stem cell properties, as GPD2 knockdown reduces sphere formation ability in both hepatocellular carcinoma and neuroblastoma cell lines 4. Additionally, GPD2 influences platelet function through ROS/NF-κB/P2Y12 signaling pathways, with hypermethylation of its promoter affecting coagulation function and bleeding risk 5. GPD2 expression is upregulated in various cancers and associated with poor prognosis, making it a potential therapeutic target 36.