GDPD3 is a lysophospholipase D enzyme that hydrolyzes lysoglycerophospholipids to generate lysophosphatidic acid (LPA) and corresponding amines, with preference for lyso-PAF, lysophosphatidylcholine, and N-acylethanolamine lysophospholipids 1. It does not display classical glycerophosphodiester phosphodiesterase activity 1. Mechanistically, GDPD3 functions as a rate-limiting enzyme in hepatic lipid metabolism by producing LPA, a key intermediate in the glycerol phosphate pathway that generates over 90% of liver triacylglycerols 2. GDPD3 also regulates epithelial-mesenchymal transition (EMT) and tumor progression through the LPA/LPAR1/AKT signaling axis 3. DISEASE RELEVANCE: GDPD3 overexpression promotes non-alcoholic fatty liver disease, with increased hepatic GDPD3 mRNA levels observed in patients with hepatic steatosis 2. GDPD3 is significantly upregulated in prostate adenocarcinoma, where knockdown inhibits tumor cell proliferation, invasion, and migration 3. Additionally, GDPD3 is among core aging-related genes upregulated in aged COPD patients 4, and serves as a biomarker for predicting chemotherapy response in muscle-invasive urothelial carcinoma 5. CLINICAL SIGNIFICANCE: GDPD3 represents a potential therapeutic target for managing hepatic steatosis and prostate cancer progression, while offering prognostic and predictive utility in multiple disease contexts.