The phospholipase A and acyltransferase (PLAAT) family is a group of structurally related proteins that are conserved among vertebrates. In humans, the family comprises five members (PLAAT1-5), which share common domain structures, and functions as phospholipase A/A and acyltransferase enzymes. Regarding acyltransferase activities, PLAATs produce N-acyl-phosphatidylethanolamines, which serve as the precursor of bioactive N-acylethanolamines (NAEs). Recent evidence strongly suggests that PLAAT proteins play a crucial role in maintaining homeostasis in various organelles, such as the endoplasmic reticulum, lysosomes, mitochondria, and peroxisomes. In this process, PLAAT proteins bind to organelles and degrade them in an enzyme activity-dependent manner. Their physiological significance was revealed by the inability of PLAAT-deficient animals to degrade organelles during the maturation of the eye lens, resulting in the development of cataracts. Furthermore, the deficiency of PLAAT1, 3, and 5 in mice caused resistance to high-fat diet-induced fatty liver, the lean phenotype represented by a marked decrease in adipose tissue mass, and the exacerbation of testicular inflammation due to decreased levels of anti-inflammatory NAEs, respectively. In addition, human PLAAT3 was identified as a causative gene for lipodystrophy. We herein provide an overview of the molecular and biological properties of PLAAT proteins.
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The PLAAT family as phospholipid-related enzymes.
Prog Lipid Res
March 2025
Department of Biochemistry, Kagawa University School of Medicine, 1750-1 Ikenobe, Miki, Kagawa 761-0793, Japan. Electronic address:
The phospholipase A and acyltransferase (PLAAT) family is a group of structurally related proteins that are conserved among vertebrates. In humans, the family comprises five members (PLAAT1-5), which share common domain structures, and functions as phospholipase A/A and acyltransferase enzymes. Regarding acyltransferase activities, PLAATs produce N-acyl-phosphatidylethanolamines, which serve as the precursor of bioactive N-acylethanolamines (NAEs).
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Biochim Biophys Acta Mol Cell Biol Lipids
March 2025
Department of Biochemistry, Kagawa University School of Medicine, Kagawa, Japan. Electronic address:
Article Synopsis
- N-Acylethanolamines (NAEs) are lipid mediators important for reducing inflammation and suppressing appetite, with palmitoylethanolamide (PEA) and arachidonoylethanolamide (AEA) interacting with specific receptors.
- The enzyme PLAAT5 is highlighted as crucial for producing NAEs in testes, as research using PLAAT5-deficient mice revealed a significant drop in NAE levels and their associated anti-inflammatory effects.
- Inflammation in testicular tissue was exacerbated in PLAAT5-deficient mice but could be mitigated by PEA and AEA, indicating that these compounds could provide protective roles through their receptor pathways.
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