PLA2G4E in health and disease : insights from omics and functional analyses

Čater, Maša (author), Šimon, Martin (author), Morton, Nicholas M. (author), Kunej, Tanja (author), Horvat, Simon (author)

The phospholipase A2 (PLA2) enzyme superfamily has been extensively studied, but omprehensive reviews on cytosolic phospholipase A2 group IVE (PLA2G4E) remain scarce, limiting our understanding of its role in lipid metabolism and disease. Our review synthesizes current findings on the human PLA2G4E gene and its murine ortholog Pla2g4e, drawing from multi-omics analyses and a range of functional studies. Pla2g4e exhibits distinct expression patterns across tissues, suggesting potential tissue-specific roles. In addition to its phospholipase activity, PLA2G4E exhibits N-acyltransferase activity and responds to calcium influx. Emerging evidence suggests possible involvement in metabolic disorders such as obesity and diabetes, particularly through effects on glucose uptake and insulin sensitivity. PLA2G4E has been implicated in the synthesis of N-acylethanolamines with potential effects on energy homeostasis, stress adaptation, neuronal signaling, pain perception, cognition, and motor coordination. Genomic and preliminary functional evidence further point to possible roles in immune regulation and neurobiology, with some associations reported in neurodegenerative diseases such as Alzheimer’s disease. Comprehensive insights into the biological roles of PLA2G4E are essential for clarifying its enzymatic functions and potential involvement in disease mechanisms; however, further experimental and clinical studies are needed to substantiate these emerging associations and assess its therapeutic potential.

• Language: English
• Keywords: phospholipases, lipid metabolism, muscles, adipose tissue, fatty acid metabolism, obesity, diabetes, N-acylethanolamine
• Work type: Article
• Typology: 1.02 - Review Article
• Organization: BF - Biotechnical Faculty
• Publication status: Published
• Publication version: Version of Record
• Publication date: 01.11.2025
• Year: 2025
• Number of pages: 20 str.
• Numbering: Vol. 100, [article no.] ǂ101359
• PID: 20.500.12556/RUL-175995
• UDC: 575
• ISSN on article: 1873-2194
• DOI: 10.1016/j.plipres.2025.101359
• COBISS.SI-ID: 257136131
• Publication date in RUL: 17.11.2025

Record is a part of a journal

• Title: Progress in lipid research
• Publisher: Elsevier
• ISSN: 1873-2194
• COBISS.SI-ID: 23276293

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: genetika, geni, PLA2G4E, debelost, diabetes, biokemija

Projects

• Funder: ARIS - Slovenian Research and Innovation Agency
• Project number: J4-2548-2020
• Name: Vpliv RNA variant na fenotipsko raznolikost pri živalskih modelih

• Funder: ARIS - Slovenian Research and Innovation Agency
• Project number: P4-0220-2020
• Name: Primerjalna genomika in genomska biodiverziteta