In the present study, 3×Tg-AD mice exhibited a pronounced downregulation of the 2-arachidonoylglycerol (2-AG) production machinery, specifically diacylglycerol lipase β (Daglb), along with reduced Dagla/Mgll and Daglb/Mgll ratios, indicating impaired capacity for 2-AG synthesis relative to its degradation. Here, MGLL is linked to Alzheimer disease.