Pex2, also known as peroxisomal E3 ubiquitin ligase peroxin 2, is a crucial gene in peroxisomal-related processes. It functions as an E3 ubiquitin ligase, playing a key role in pexophagy (the autophagic degradation of peroxisomes), peroxisomal protein import, and lipid metabolism regulation. Pex2-related pathways are significant for maintaining cellular homeostasis, and genetic models like knockout mice are valuable for studying its functions [1,3].

In Pex2-deficient murine models (a model for Zellweger syndrome), there are severe consequences. Embryonic lethality is observed, along with widespread neuronal lipidosis in the brain. Biochemically, very long chain fatty acids accumulate, and plasmalogens are deficient in various tissues. DHA levels are reduced in the brain and all postnatal tissues. Cholesterol homeostasis is also disrupted, with decreased plasma and liver cholesterol levels, up-regulated SREBP-2 gene expression, and altered activities of cholesterol biosynthetic enzymes. Moreover, peroxisome-dependent pathways such as bile acid biosynthesis are affected [2,4,5].

In conclusion, Pex2 is essential for peroxisomal function, lipid and cholesterol metabolism, and normal development. The Pex2 knockout mouse models have been instrumental in revealing its role in Zellweger syndrome-like phenotypes, highlighting its importance in understanding the pathogenesis of peroxisomal biogenesis disorders.