Serine hydrolase that hydrolyzes arachidonic acid-esterified diacylglycerols (DAGs) to produce the principal endocannabinoid (eCB), 2-arachidonoylglycerol (2-AG) (PubMed:17584991, PubMed:23103940). Preferentially hydrolyzes sn-1 fatty acids from diacylglycerols (DAG) that contain arachidonic acid (AA) esterified at the sn-2 position to biosynthesize 2-AG. Has negligible activity against other lipids including monoacylglycerols and phospholipids (PubMed:17584991). Plays a key role in regulating 2-AG signaling in the central nervous system (CNS) (PubMed:20159446, PubMed:20147530, PubMed:25466252, PubMed:26668358, PubMed:26779719). Controls the activity of 2-AG as a retrograde messenger at neuronal synapses (PubMed:20159446, PubMed:20147530, PubMed:26668358). Supports axonal growth during development and adult neurogenesis (PubMed:20147530). Plays a role for eCB signaling in the physiological regulation of anxiety and depressive behaviors (PubMed:25466252). Regulates also neuroinflammatory responses in the brain, in particular, LPS-induced microglial activation (PubMed:26779719). a 1,2-diacyl-sn-glycerol + H2O = a 2-acylglycerol + a fatty acid + H(+) 1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycerol + H2O = 2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + H(+) + octadecanoate 1,2-di-(9Z-octadecenoyl)-sn-glycerol + H2O = (9Z)-octadecenoate + 2-(9Z-octadecenoyl)-glycerol + H(+) 1-(9Z-octadecenoyl)-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycerol + H2O = (9Z)-octadecenoate + 2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + H(+) 1-(9Z-octadecenoyl)-2-octadecanoyl-sn-glycerol + H2O = (9Z)-octadecenoate + 2-octadecanoylglycerol + H(+) 1-(9Z-octadecenoyl)-2-(9Z,12Z-octadecadienoyl)-sn-glycerol + H2O = (9Z)-octadecenoate + 2-(9Z,12Z-octadecadienoyl)-glycerol + H(+) 1-(9Z-octadecenoyl)-2-O-(5Z,8Z,11Z,14Z-eicosatetraenyl)-sn-glycerol + H2O = (9Z)-octadecenoate + 2-O-(5Z,8Z,11Z,14Z)-eicosatetraenylglycerol + H(+) Inhibited by 1,2,3-triazole urea covalent inhibitor KT172, DH376 and DO34 (PubMed:23103940, PubMed:26668358). Inhibited by p-hydroxy-mercuri-benzoate and HgCl(2), but not to PMSF. Also inhibited by RHC80267. Diacylglycerol lipase activity is inhibited by the phosphorylation of Ser-784 and Ser-810 by CAMK2A (By similarity). Interacts (via C-terminal) with CAMK2A; leading to the phosphorylation and inhibition of DAGLA enzymatic activity (PubMed:23502535). Interacts (via PPXXF motif) with HOMER1 and HOMER2; this interaction is required for DAGLA membrane localization (PubMed:17584991). Cycles between the cell surface and an intracellular endosomal compartment. Internalized by early endosomes via a clathrin-independent pathway before transport back to the postsynaptic membrane surface in a PKC-dependent manner. Highly expressed by principal cells in the hippocampus. In embryonic brains, it is present in axonal tracts, while in adults it localizes to dendritic fields, correlating with the developmental change in requirement for 2-AG synthesis from the pre- to the postsynaptic compartment. Concentrated in heads of dendritic spines throughout the hippocampal formation. Highly compartmentalized into a wide perisynaptic annulus around the postsynaptic density of axospinous contacts but not intrasynaptically (at protein level). Phosphorylated at Ser-784 and Ser-810 by CAMK2A; phosphorylation by CAMK2A inhibits diacylglycerol lipase activity. Deficient mice are viable, fertile and display normal physiological behaviors (PubMed:20159446, PubMed:20147530). Deficient mice show 80-90% reductions in brain 2-AG as well as the downstream product arachidonic acid (AA), in particular in neurons and astrocytes (PubMed:20159446, PubMed:20147530, PubMed:26779719, PubMed:25466252). The endocannabinoid-mediated retrograde synaptic suppression of neurotransmitter release is absent in the cerebellum, hippocampus, and striatum of knockout mice (PubMed:20159446, PubMed:20147530). In addition, reduction in adult neurogenesis is observed in deficient mice in both the hippocampus and the subventricular zone (PubMed:20147530). DAGLA deletion increases anxiety-like and depressive behaviors (PubMed:25466252). Reduction in LPS-stimulated neuroinflammation is also observed in knockout mice (PubMed:26779719). Belongs to the AB hydrolase superfamily. Lipase family.