Pex2, also known as peroxisomal E3 ubiquitin ligase peroxin 2, is a crucial gene in peroxisome-related functions. It functions as an E3 ubiquitin ligase, playing a key role in processes such as pexophagy, peroxisomal protein import, and the regulation of lipid metabolism. Genetic models, especially knockout mouse models, have been valuable in studying its functions [1,3-4,7-9].

In a Pex2 knockout mouse model, which mimics Zellweger syndrome, there are significant pathologic and biochemical consequences. Neuronal migration is delayed in the cerebral cortex, and severe cerebellar defects occur. Biochemically, there is an accumulation of very long chain fatty acids, deficient plasmalogens, and reduced docosahexaenoic acid levels in various tissues. Cholesterol homeostasis is also disturbed, with changes in cholesterol biosynthesis, bile acid synthesis, and the expression of related enzymes and transporters. Moreover, peroxisome deficiency in these mice activates hepatic endoplasmic reticulum stress pathways and dysregulates the endogenous sterol response mechanism [1,2,3].

In conclusion, Pex2 is essential for peroxisome-related functions, including lipid metabolism and protein import. The Pex2 knockout mouse models have provided valuable insights into the pathogenesis of Zellweger syndrome and the role of Pex2 in maintaining cholesterol homeostasis and normal tissue function. Understanding Pex2 helps in unravelling the mechanisms underlying peroxisomal-related diseases and may offer potential therapeutic targets.