DAGLB (diacylglycerol lipase beta) is a calcium-dependent lipase that catalyzes the hydrolysis of arachidonic acid-esterified diacylglycerols to produce 2-arachidonoylglycerol (2-AG), the principal endocannabinoid in the brain 1. DAGLB preferentially hydrolyzes DAGs at the sn-1 position and also functions as a polyunsaturated fatty acid-specific triacylglycerol lipase in macrophages. The enzyme plays a critical role in regulating 2-AG and arachidonic acid pools utilized by cyclooxygenase enzymes to generate lipid mediators of inflammatory responses in macrophages and microglia 2. In the nervous system, DAGLB is essential for normal neuronal function. AP-4 vesicles transport DAGLB to axons where 2-AG signaling drives axonal growth 3. Loss-of-function mutations in DAGLB cause autosomal recessive early-onset Parkinsonism, with DAGLB serving as the main 2-AG synthase in substantia nigra dopaminergic neurons 4. Reduced nigral 2-AG levels correlate with motor dysfunction, and pharmacological elevation of 2-AG rescues dopamine release and locomotor deficits 45. Beyond neurological functions, DAGLB variants influence metabolic traits. A genetic variant modifying DAGLB expression associates with serum HDL-cholesterol levels 6, and DAGLB is implicated in mechanisms uncoupling excess adiposity from cardiometabolic complications 7.