# PLA2G4F

## Overview
PLA2G4F is a gene located in the human genome that encodes the enzyme phospholipase A2 group IVF (cPLA2ζ). This enzyme is a member of the cytosolic phospholipase A2 family, which plays a pivotal role in the metabolism of phospholipids by catalyzing the hydrolysis of glycerophospholipids to release arachidonic acid, a precursor for various bioactive lipid mediators. Phospholipase A2 group IVF is distinct in its expression and function across different tissues, contributing to various physiological and pathological processes. The protein is particularly significant in the context of cardiac function and intervertebral disc health, where it influences inflammatory responses and cellular metabolism (Tan2023Role; Kita2019Cytosolic).

## Function
PLA2G4F, encoding the cPLA2ζ enzyme, plays a crucial role in mitochondrial function within non-failing human hearts. This enzyme is primarily responsible for the calcium-activated release of arachidonic acid (AA) from cardiac mitochondria. The released AA is then utilized in the production of heart-protective epoxyeicosatetraenoic acids (EETs), which are significant in maintaining normal cardiac function. This protective role contrasts with other phospholipase A2 enzymes, such as iPLA2γ, which are associated with the production of toxic hydroxyeicosatetraenoic acids (HETEs) in failing hearts (Kita2019Cytosolic). The specific activities and mechanisms of PLA2G4F suggest its involvement in crucial cellular processes that contribute to heart health and the prevention of cardiac diseases. However, the understanding of PLA2G4F's roles and mechanisms is still emerging, indicating a need for further research to fully elucidate its functions and potential therapeutic implications in cardiac physiology (Kita2019Cytosolic).

## Clinical Significance
PLA2G4F, a gene encoding phospholipase A2 group IVF, has been implicated in the pathology of intervertebral disc degeneration (IVDD). Research utilizing advanced machine learning algorithms identified PLA2G4F as a significant biomarker for IVDD, suggesting that alterations in its expression or function could be linked to the progression of this condition (Tan2023Role). The gene's role in arachidonic acid metabolism, crucial for the cellular processes of nucleus pulposus cells and the immune microenvironment of the intervertebral disc, underscores its potential impact on IVDD pathology (Tan2023Role).

In contrast, a study on the association between PLA2G4F and schizophrenia in a Han Chinese population found no significant link between specific polymorphisms in the gene and the disorder. This indicates that while PLA2G4F may play a critical role in certain inflammatory and degenerative diseases, its impact on neurological conditions such as schizophrenia is not supported by current genetic evidence (Yu2010Genetic).

These findings highlight the clinical significance of PLA2G4F in the context of inflammatory and degenerative diseases, particularly IVDD, while also demonstrating the complexities of gene-disease associations across different conditions.


## References


[1. (Yu2010Genetic) Qiong Yu, Xiang-Fei Meng, Jie-Ping Shi, and Ya-Qin Yu. Genetic association between the polymorphism of cytosolic pla2 gene family and schizophrenia. Frontiers of Medicine in China, 4(1):101–105, February 2010. URL: http://dx.doi.org/10.1007/s11684-010-0017-6, doi:10.1007/s11684-010-0017-6. (0 citations) 10.1007/s11684-010-0017-6](https://doi.org/10.1007/s11684-010-0017-6)

[2. (Tan2023Role) Jianye Tan, Meiling Shi, Bin Li, Yuan Liu, Shengzhong Luo, and Xigao Cheng. Role of arachidonic acid metabolism in intervertebral disc degeneration: identification of potential biomarkers and therapeutic targets via multi-omics analysis and artificial intelligence strategies. Lipids in Health and Disease, November 2023. URL: http://dx.doi.org/10.1186/s12944-023-01962-5, doi:10.1186/s12944-023-01962-5. (2 citations) 10.1186/s12944-023-01962-5](https://doi.org/10.1186/s12944-023-01962-5)

[3. (Kita2019Cytosolic) Yoshihiro Kita, Hideo Shindou, and Takao Shimizu. Cytosolic phospholipase a2 and lysophospholipid acyltransferases. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 1864(6):838–845, June 2019. URL: http://dx.doi.org/10.1016/j.bbalip.2018.08.006, doi:10.1016/j.bbalip.2018.08.006. (76 citations) 10.1016/j.bbalip.2018.08.006](https://doi.org/10.1016/j.bbalip.2018.08.006)