DGKD (diacylglycerol kinase delta) is a lipid kinase that catalyzes the phosphorylation of diacylglycerol (DAG) to phosphatidic acid (PA), functioning as a molecular switch between distinct signaling pathways with opposing biological effects 12. By regulating DAG levels, DGKD modulates PKC and EGF receptor signaling and may regulate clathrin-dependent endocytosis 3. DGKD serves as a critical calcium-sensing receptor (CaSR) signaling partner 4. In kidney stone disease (KSD) pathogenesis, DGKD genetic variants impair CaSR signal transduction, affecting calcium and phosphate homeostasis; reduced DGKD expression correlates with increased urinary calcium excretion and elevated KSD risk 54. Pharmacological CaSR modulation via cinacalcet can rescue impaired signaling caused by KSD-associated DGKD variants, suggesting potential therapeutic strategies 54. DGKD variants have been investigated in Parkinson disease with inconsistent population-specific associations 6. DGKD is implicated in malignant meningioma progression and pediatric acute lymphoblastic leukemia through novel fusion gene formation (SFMBT2::DGKD) 78. Additionally, DGKD expression relates to sepsis-induced cardiomyopathy pathogenesis 9.