Diacylglycerol lipase alpha (DAGLα)

Diacylglycerol lipase alpha (DAGLα) is a membrane-associated enzyme that hydrolyzes diacylglycerol to generate 2-arachidonoylglycerol (2-AG), the most abundant endocannabinoid in the brain and peripheral tissues. By regulating 2-AG levels, DAGLα plays a central role in retrograde signaling at synapses, modulating neurotransmitter release through activation of cannabinoid CB1 and CB2 receptors. It is crucial for neuronal development, axon guidance, generation and migration of new neurons, and maintenance of synaptic plasticity. Outside the nervous system, DAGLα regulates lipid signaling, arachidonic acid metabolism, and inflammation. Dysregulation of DAGLα is implicated in neurodegenerative diseases and cancer, notably by promoting tumor proliferation, invasiveness, and resistance to targeted therapies. The enzyme is a focus of ongoing drug discovery, targeting its role in endocannabinoid signaling and pathological processes.

Other names

Diacylglycerol lipaseDAG lipaseDAGLDGLDAGLAFMP30Neural stem cell-derived dendrite regulator

Inhibition leads to reduced 2-AG production and decreased endocannabinoid signaling; Modulation of neurotransmitter release via CB1/CB2 receptor regulation; Inhibition impacts tumor growth and drug resistance (in hepatocellular carcinoma models).