Diacylglycerol kinase epsilon (DGKE)

Diacylglycerol kinase epsilon (DGKE) is a membrane-bound lipid kinase that catalyzes the phosphorylation of diacylglycerol (DAG) to phosphatidic acid (PA), regulating essential cell signaling pathways, particularly the phosphatidylinositol cycle. DGKE displays highly selective substrate specificity for DAG species bearing an arachidonoyl chain and lacks regulatory domains present in other DGK isoforms, conferring unique biochemical properties. Deficiency or pathogenic mutations in DGKE underlie atypical hemolytic-uremic syndrome (aHUS) and nephrotic syndromes, driving renal dysfunction and early-onset vascular complications. DGKE is viewed as a promising therapeutic target for renal and metabolic diseases, though subtype-specific inhibitors or activators remain under development. Disease management is complex and can include plasma therapy, complement inhibitors, and immunosuppressants, with inconsistent benefits for patients carrying DGKE mutations.

Other names

DAG kinase epsilonDGK-epsilonDAGK5DAGK6Diglyceride kinase epsilondiacylglycerol kinase, epsilon 64kDaAHUS7NPHS7

Inhibition or modulation of DGKE enzyme activity may impact DAG/PA balance, affect downstream protein kinase C signaling, and modify glomerular thrombosis risk. Complement inhibition (eculizumab) acts indirectly in related syndromes.