DAGLA encodes diacylglycerol lipase alpha, a serine hydrolase that catalyzes the hydrolysis of arachidonic acid-esterified diacylglycerols to produce 2-arachidonoylglycerol (2-AG), the principal endocannabinoid 1. The enzyme preferentially cleaves sn-1 fatty acids from diacylglycerols containing arachidonic acid at the sn-2 position, playing a crucial role in endocannabinoid signaling within the central nervous system 1. DAGLA is essential for regulating 2-AG-mediated retrograde suppression at synapses and supports neurogenesis and axonal growth. Disease relevance includes truncating variants in DAGLA's last exon causing neuro-ocular syndrome 2, characterized by developmental delay, ataxia, and complex oculomotor abnormalities with paroxysmal nystagmus 1. These variants preserve enzymatic activity but cause perinuclear protein aggregation, suggesting haploinsufficiency or dominant-negative effects 1. Additionally, DAGLA autoantibodies are associated with rapidly progressive cerebellar ataxia and treatment-refractory autoimmune encephalitis 23. Beyond neurological functions, DAGLA promotes hepatocellular carcinoma progression by enhancing YAP activity and induces resistance to lenvatinib therapy 4. The enzyme also exhibits sex-specific roles in astrocytic regulation of hedonic feeding behavior 5.