Diacylglycerol lipase-beta (DAGLB)

Diacylglycerol lipase-beta (DAGLB) is a transmembrane serine hydrolase comprising 672 amino acids with a core α/β hydrolase catalytic domain and four transmembrane regions[3][4]. It selectively hydrolyzes DAG at the sn-1 position to generate 2-arachidonoylglycerol, the most abundant endogenous agonist for CB1 and CB2 cannabinoid receptors, and regulates tissue-specific synthesis of 2-AG. In immune cells such as macrophages and microglia, DAGLB controls bioenergetics, inflammation, and pain response via interactions with the AMPK signaling pathway and downstream eicosanoid synthesis[5]. Mutations or deficiency in DAGLB have been implicated in pathogenesis of neurodegenerative disorders such as Parkinsonism, impaired synaptic signaling, and increased susceptibility to inflammation or hepatic lipid accumulation[1][4]. Pharmacological inhibition of DAGLB suppresses peripheral prostaglandin and endocannabinoid signaling, showing therapeutic promise in models of chronic pain and inflammation without some of the adverse effects typical of NSAIDs[5][8].

Other names

Diacylglycerol lipase‐βDAGL-betaDGL-betaDAGLBETAKCCR13LPUFA-specific triacylglycerol lipasesn1-specific diacylglycerol lipase beta

Inhibition of DAGLβ blocks 2-AG synthesis, reducing cannabinoid and prostaglandin signaling, which suppresses inflammation and pain. DAGLB inhibition modulates AMPK signaling, which can alter bioenergetics and suppress hyperexcitability in pain models.