Peds1, also known as plasmanylethanolamine desaturase 1 (PEDS1) and TMEM189, is an enzyme crucial for plasmalogen biosynthesis. Plasmalogens are glycerophospholipids with a vinyl ether bond, and Peds1 functions to introduce this double bond into plasmanylethanolamine phospholipids [2,3,4,7]. Ether lipids, including plasmalogens, play roles in membrane organization, fluidity, signaling, and antioxidative functions, and abnormal levels are associated with various human pathologies [2,8].

Peds1 -deficient zebrafish larvae display delayed development, increased basal inflammation, normal hematopoietic stem and progenitor cell emergence, and cell-autonomous myeloid cell apoptosis. In inflammation models, they show impaired inflammation resolution, tissue regeneration, increased cytokine expression, and elevated ROS levels. Exogenous plasmalogen can mitigate some of these effects [1]. Peds1-knockout mice exhibit a growth phenotype and striking changes in lipid composition, with a strong reduction of plasmenyl lipids and a concomitant massive accumulation of plasmanyl lipids [3]. A single mutation (aspartate 100) in murine Peds1 leads to a total loss of its enzymatic activity [4]. In humans, the Peds1 rs6020298 GG genotype and G allele are significantly associated with an increased risk of developing Long COVID [5]. TMEM189 (Peds1) negatively regulates the proteostasis of ULK1 and autophagy activity, and its deficiency inhibits the tumorigenicity of gastric cancer [6].

In conclusion, Peds1 is essential for plasmalogen biosynthesis, and its deficiency in model organisms reveals its importance in myeloid cell biology, inflammation, lipid metabolism, autophagy, and disease-related processes such as Long COVID and tumorigenesis. The study of Peds1 through gene-knockout models provides valuable insights into its biological functions and potential implications for human health.