[4] By searching with BLAST for the previously sequenced microorganism DAGL,[5] Bisogno et al discovered two distinct mammalian isoforms, designated DAGLα (DAGLA) and DAGLβ (DAGLB).

[6] As a result, much effort has been made toward investigating the mechanisms of action and the therapeutic potential of the system's receptors, endogenous ligands, and enzymes like DAGLα and DAGLβ.

[1] Initially, histidine deprotonates serine forming a strong nucleophilic alkoxide, which attacks the carbonyl of the acyl group at the sn-1 position of DAG.

[6] Endocannabinoid signaling via these receptors is involved in core body temperature control, inflammation, appetite promotion, memory formation, mood and anxiety regulation, pain relief, addiction reward, neuron protection, and more.

[13][14] DAGLα is prevalent in central nervous tissues where it is primarily responsible for the on-demand production[15] of 2-AG, which is involved in retrograde synaptic suppression, regulation of axonal growth, adult neurogenesis, and neuroinflammation.

[13][14][15] DAGLβ has enriched activity in innate immune cells such as macrophages and microglia enabling regulation of 2-AG and downstream metabolic products (e.g. prostaglandins) important for proinflammatory signaling in neuroinflammation and pain.

[21] However, DAGLα inhibition has also been associated reduction in neuroplasticity, increased anxiety and depression, seizures, and other neuropsychiatric side effects due to drastic alteration of brain lipids.

[15][21] In vivo experiments show that selectively inhibiting DAGLβ has the potential to be a powerful anti-inflammatory therapy by suppressing the production of the proinflammatory molecules arachidonic acid, prostaglandins, tumor necrosis factor α in macrophages and dendritic cells.