CYP2U1 is a cytochrome P450 monooxygenase primarily expressed in brain and thymus tissues 1 that catalyzes omega- and omega-1 hydroxylation of long-chain fatty acids, particularly arachidonic acid 1. The enzyme uses molecular oxygen to hydroxylate substrates, with electrons provided by NADPH via cytochrome P450 reductase 1. Beyond arachidonic acid, CYP2U1 metabolizes docosahexaenoic acid and leukotriene B4, an important inflammatory mediator 2. CYP2U1 also catalyzes C-2 oxidation of N-arachidonoyl-serotonin, an endocannabinoid, producing less bioactive metabolites 3. By generating bioactive eicosanoid derivatives, CYP2U1 likely modulates fatty acid signaling pathways critical for neuronal and immune function 1. CYP2U1 mutations cause hereditary spastic paraplegia type 56 (SPG56), characterized by progressive lower extremity weakness and spasticity due to corticospinal tract degeneration 4. Loss of CYP2U1 function disrupts mitochondrial architecture and bioenergetics 2. Recent studies identify vitamin B2 as a CYP2U1 substrate and show that folate supplementation prevents neurodegeneration in CYP2U1-deficient mice, suggesting therapeutic potential 5. CYP2U1 expression is elevated in alcoholics and smokers in brain regions mediating addiction 6, indicating additional roles in neuroactive drug metabolism.