ABHD2 is a progesterone-dependent acylglycerol lipase that catalyzes hydrolysis of endocannabinoid arachidonoylglycerol (AG) to glycerol and arachidonic acid 1. The protein functions as a ligand-activated enzyme, with progesterone binding activating its lipase activity against both monoacylglycerols (1AG and 2AG) and additional ester substrates including acetyl, butanoate, and hexadecanoate esters 2. ABHD2 plays a critical role in male fertility through sperm capacitation, wherein progesterone-induced degradation of 2AG—an inhibitor of the calcium channel CatSper—permits calcium influx and sperm activation 1. The acrosome reaction is similarly regulated by ABHD2, as selective inhibitors reduce this progesterone-stimulated process 3. Beyond reproduction, ABHD2 maintains alveolar architecture and regulates airway remodeling in COPD by modulating TGF-β signaling and epithelial-mesenchymal transition 4. Clinically, ABHD2 is upregulated in multiple cancers (breast, lung, prostate, hepatocellular carcinoma, and cervical cancer) where it promotes cell proliferation, migration, invasion, and resistance to apoptosis through lipid metabolism pathways 5678. ABHD2 expression in prostate cancer correlates with Gleason score and poor prognosis 5. These findings establish ABHD2 as both a reproductive regulator and oncogenic target with therapeutic potential.