DAGLB encodes a diacylglycerol lipase that catalyzes hydrolysis of arachidonic acid-esterified diacylglycerols to produce 2-arachidonoylglycerol (2-AG), the principal endocannabinoid in brain tissue. The enzyme preferentially acts at the sn-1 position in a calcium-dependent manner and plays a key role in regulating 2-AG and arachidonic acid pools used by cyclooxygenase enzymes to generate lipid mediators of macrophage and microglial inflammatory responses. DAGLB has emerged as a significant locus in endocannabinoid-related neurodegenerative disease. Loss-of-function variants in DAGLB are associated with early-onset autosomal recessive Parkinsonism across multiple populations, including Chinese, Algerian, and Japanese cohorts 12. In murine studies, Daglb deficiency in nigral dopaminergic neurons reduced substantia nigra 2-AG levels and impaired locomotor skill learning; pharmacological inhibition of 2-AG degradation rescued these deficits 3. DAGLB is also transported anterogradely to axons via AP-4 vesicles, where 2-AG signalling promotes axonal growth, and defects in AP-4-mediated transport reduce axonal DAGLB and 2-AG levels 4. Beyond neurodegeneration, DAGLB variants are associated with altered lipid metabolism. A regulatory variant near DAGLB (rs1880118) influences serum HDL-cholesterol levels through modulation of DAGLB expression in adipose tissue 5, and DAGLB is implicated in the uncoupling of excess adiposity from cardiometabolic risk 6. These findings position DAGLB as a critical node in endocannabinoid signalling and metabolic regulation.