SGPL1 and Huntington disease: Research by Pepe et al. demonstrated that the inhibitor 2-acetyl-5-tetrahydroxybutyl imidazole (THI), an inhibitor of the sphingosine-1-phosphate (S1P) degradative enzyme SGPL1, significantly reduces myelin damage in HD and restores myelin marker proteins in HD models, supporting the dysregulated lipid or fatty acid mechanism in HD.63,64 These findings highlight the importance of lipid metabolism in myelin integrity and suggest potential therapeutic targets for addressing myelin impairment in HD through modulation of lipid pathways.