Diacylglycerol lipase (DAGL)

Diacylglycerol lipase, or DAGL, is the enzyme that makes the endocannabinoid 2-arachidonoylglycerol by cutting a fatty acid from a membrane lipid called diacylglycerol.

There are two forms, DAGL-alpha and DAGL-beta. DAGL-alpha sits in the membrane of the receiving side of a synapse, positioned so that when a neuron becomes active and calcium enters, it can produce 2-AG on demand. The newly made 2-AG then crosses the synapse to CB1 receptors on the sending neuron and suppresses further neurotransmitter release. DAGL-beta is more prominent in immune cells and in the liver, where its 2-AG output feeds into inflammatory lipid pathways.

Animals lacking DAGL-alpha have very low brain 2-AG and lose most of the retrograde signaling that defines the endocannabinoid system, which is how the enzyme's role was confirmed. The term appears in advanced discussions of endocannabinoid tone and in research on enzyme inhibitors as experimental tools; CBD has no established direct action on DAGL, and the enzyme is mentioned here mainly for context.