Pcyt2, also known as phosphatidylethanolamine cytidyltransferase (ECT), is a key enzyme in the CDP-ethanolamine pathway for phosphatidylethanolamine (PE) synthesis. PE is one of the most abundant membrane lipids, and thus Pcyt2 is crucial for maintaining membrane lipid bilayer structure and stability, as well as cellular bioenergetics [1,2,5].

In genetic models, pcyt2 -mutant zebrafish and muscle -specific Pcyt2 -knockout mice show phenotypes like failure to thrive, progressive muscle weakness, and accelerated ageing, indicating Pcyt2's importance in muscle health [1]. Heterozygous deletion of Pcyt2 in mice causes age -dependent development of nonalcoholic steatohepatitis and insulin resistance [2]. Genetic deletion of Pcyt2 in activated T cells impairs the differentiation of TFH cells and reduces humoral immune responses [4]. In Saarlooswolfdogs, a homozygous missense variant in Pcyt2 leads to progressive retinal, central, and peripheral neurodegeneration [3]. In humans, mutations in Pcyt2 disrupt etherlipid biosynthesis and cause a complex hereditary spastic paraplegia [5].

In summary, Pcyt2 plays fundamental roles in muscle health, lipid metabolism, immune responses, and neural development. Model -based research, especially Pcyt2 knockout mouse models, has revealed its significance in diseases such as muscle dystrophy, non -alcoholic steatohepatitis, and certain neurodegenerative and neuromuscular disorders, providing insights into disease mechanisms and potential therapeutic targets.

References:

1. Cikes, Domagoj, Elsayad, Kareem, Sezgin, Erdinc, Banka, Siddharth, Penninger, Josef M. 2023. PCYT2-regulated lipid biosynthesis is critical to muscle health and ageing. In Nature metabolism, 5, 495-515. doi:10.1038/s42255-023-00766-2. https://pubmed.ncbi.nlm.nih.gov/36941451/

2. Grapentine, Sophie, Singh, Rathnesh K, Basu, Poulami, Dolinsky, Vernon W, Bakovic, Marica. 2022. Pcyt2 deficiency causes age-dependant development of nonalcoholic steatohepatitis and insulin resistance that could be attenuated with phosphoethanolamine. In Scientific reports, 12, 1048. doi:10.1038/s41598-022-05140-y. https://pubmed.ncbi.nlm.nih.gov/35058529/

3. Christen, Matthias, Oevermann, Anna, Rupp, Stefan, Lohi, Hannes, Leeb, Tosso. 2024. PCYT2 deficiency in Saarlooswolfdogs with progressive retinal, central, and peripheral neurodegeneration. In Molecular genetics and metabolism, 141, 108149. doi:10.1016/j.ymgme.2024.108149. https://pubmed.ncbi.nlm.nih.gov/38277988/

4. Fu, Guotong, Guy, Clifford S, Chapman, Nicole M, Jackowski, Suzanne, Chi, Hongbo. 2021. Metabolic control of TFH cells and humoral immunity by phosphatidylethanolamine. In Nature, 595, 724-729. doi:10.1038/s41586-021-03692-z. https://pubmed.ncbi.nlm.nih.gov/34234346/

5. Vaz, Frédéric M, McDermott, John H, Alders, Mariëlle, Engelen, Marc, Banka, Siddharth. . Mutations in PCYT2 disrupt etherlipid biosynthesis and cause a complex hereditary spastic paraplegia. In Brain : a journal of neurology, 142, 3382-3397. doi:10.1093/brain/awz291. https://pubmed.ncbi.nlm.nih.gov/31637422/