Diacylglycerol lipases (DGLs) mainly catalyze “on-demand” biosynthesis of bioactive monoacylglycerols (MAGs) with different long fatty acyl chains, including 2-arachidonoylglycerol (2-AG), 2-linoleoylglycerol (2-LG), 2-oleoylglycerol (2-OG) and 2-palmitoylglycerol (2-PG). Enzymatic characterization of DGLs, their expression and distribution, and functional features has been elucidated from microorganisms to mammals in some extent. In mammals, biosynthesis, degradation and metabolism of these bioactive lipids intertwine and form a complicated biochemical pathway to affect the mammal neuromodulation of central nervous system and also other physiological processes in most peripheral organs and non-nervous tissue cells, and yet we still do not know if the neuromodulatory role of mammal DGL and MAGs is similar to invertebrates. Tracing the evolutionary history of DGLs from microorganisms to vertebrates will be an essential method to infer DGL and MAG research in organisms. In this review, we give an exhaustive explanation of the ancestral origin, divergence and evolutionary pattern through systemic searching of DGL orthologs in different species. Finally, we also summarize our recent work on the structural and functional studies of DGL in order to explore usage of DGLs in industry and the development of inhibitors for clinical intervention.

二酰基甘油脂肪酶（DGLs）主要催化具有不同长脂肪酰基链的生物活性单酰基甘油（MAGs）的“按需”生物合成，其中包括2-花生四烯酰基甘油（2-AG），2-亚油酰甘油（2-LG），2-油酰甘油（2 -OG）和2-棕榈酰甘油（2-PG）。从微生物到哺乳动物，已经阐明了DGL的酶学表征，它们的表达和分布以及功能特征。在哺乳动物中，这些生物活性脂质的生物合成，降解和代谢交织在一起，并形成复杂的生化途径，以影响哺乳动物中枢神经系统的神经调节以及大多数外围器官和非神经组织细胞中的其他生理过程，但我们仍然没有知道哺乳动物DGL和MAG的神经调节作用是否与无脊椎动物相似。追踪DGL从微生物到脊椎动物的进化历史将是推断DGL和MAG在生物中研究的一种必不可少的方法。在这篇综述中，我们通过系统搜索不同物种的DGL直系同源物，详尽地解释了祖先的起源，发散和进化模式。最后，我们还总结了我们在DGL的结构和功能研究方面的最新工作，以探索DGL在工业中的用途以及用于临床干预的抑制剂的开发。