Monoacylglycerol lipase (MAGL) has been characterized as the main enzyme responsible for the inactivation of the most abundant brain endocannabinoid, 2-arachidonoylglycerol (2-AG). Besides this role, MAGL has progressively acquired a growing importance as an integrative metabolic hub that controls not only the in vivo levels of 2-AG but also of other monoacylglycerides and, indirectly, the levels of free fatty acids derived from their hydrolysis as well as other lipids with pro-inflammatory or pro-tumorigenic effects, coming from the further metabolism of fatty acids. All these functions have only started to be elucidated in the last years due to the progress made in the knowledge of the structure of MAGL and in the development of genetic and chemical tools. In this review we report the advances made in the field with a special focus on the last decade and how MAGL has become a promising therapeutic target for the treatment of several diseases that currently lack appropriate therapies.
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