Monoglyceride lipase

Monoglyceride lipase (MGLL) is a serine hydrolase that catalyzes the conversion of monoacylglycerides to free fatty acids and glycerol (UniProt: Q99685). It plays a key regulatory role in endocannabinoid signaling by hydrolyzing the endocannabinoid 2-arachidonoylglycerol, thereby modulating nociperception and pain perception. Additionally, MGLL regulates fatty acid-mediated signaling involved in cancer cell migration and invasion.

In the central nervous system, MGLL participates in lipid metabolism and endocannabinoid homeostasis, processes relevant to neuroinflammation and neurodegeneration. The enzyme is broadly expressed across tissues involved in lipid catabolism and cell signaling.

MGLL shows elevated abundance in Alzheimer's disease brain tissue. In human post-mortem AD brain tissue compared to age-matched controls, MGLL was upregulated with a mean log₂FC of +0.67 across one subcellular fraction in TMT-labeled quantitative proteomics analysis (Chaparral AD proteomics). This upregulation may reflect altered endocannabinoid metabolism and lipid homeostasis in the AD brain, potentially contributing to neuroinflammatory processes associated with disease pathology.