DGKE encodes diacylglycerol kinase epsilon, a membrane-bound enzyme that catalyzes the ATP-dependent phosphorylation of diacylglycerol (DAG) to phosphatidic acid (PA), thereby regulating the balance of these two opposing bioactive lipid second messengers 12. DGKE displays substrate specificity for DAG containing arachidonoyl chains at the sn-2 position, particularly those generated during phosphatidylinositol turnover 23. By controlling DAG/PA ratios, DGKE acts as a molecular switch between distinct signaling pathways with opposite cellular effects across numerous biological processes, including complex lipid biosynthesis 14. Clinically, loss-of-function mutations in DGKE cause atypical hemolytic uremic syndrome (aHUS) and nephrotic syndrome through mechanisms distinct from complement dysregulation 56. DGKE deficiency leads to a prothrombotic state with endothelial damage, thrombocytopenia, hemolytic anemia, and acute kidney injury 7. Recent evidence suggests DGKE-associated aHUS involves podocyte dysfunction with nephrotic-range proteinuria, and some patients exhibit unexpected complement activation 89. Additionally, DGKE protects against acute kidney injury through the KLF15/Klotho signaling pathway 10. These findings highlight DGKE's critical role in renal homeostasis beyond complement-mediated mechanisms, with important implications for personalized therapeutic management of aHUS 11.