Pcyt2, also known as phosphatidylethanolamine cytidyltransferase (ECT), is a key enzyme in the CDP-ethanolamine pathway for phosphatidylethanolamine synthesis. Phosphatidylethanolamine is an abundant membrane lipid, playing crucial roles in cell division, signaling, activation, autophagy, and phagocytosis [6]. Genetic models like knockout mice are valuable for studying its functions.

Pcyt2 deficiency in humans leads to severe diseases, and pcyt2-mutant zebrafish and muscle-specific Pcyt2-knockout mice mimic the phenotypes, showing failure to thrive, progressive muscle weakness, and accelerated ageing. Mechanistically, it affects cellular bioenergetics and membrane lipid bilayer in muscles [1]. In colorectal cancer, PCYT2 acts as a metastasis suppressor by increasing YAP1 phosphorylation [2]. In mice, heterozygous deletion of Pcyt2 causes age-dependent nonalcoholic steatohepatitis and insulin resistance, which can be reversed by phosphoethanolamine [3]. In Saarlooswolfdogs, a PCYT2 deficiency variant leads to progressive retinal, central, and peripheral neurodegeneration [4]. Also, genetic deletion of Pcyt2 in activated T cells impairs the differentiation of TFH cells and humoral immune responses [5]. In addition, knockdown of PCYT2 in cultured human cells increases the expression of functionally glycosylated α-dystroglycan [7].

In summary, Pcyt2 is essential for maintaining muscle health, regulating lipid biosynthesis, and is involved in various disease conditions such as muscle dystrophy, cancer, nonalcoholic steatohepatitis, neurodegeneration, and immune-related disorders. The study of Pcyt2 knockout models has significantly advanced our understanding of these disease mechanisms, providing potential therapeutic targets for treatment [1-5, 10].