Pex12

PEX12 is a gene encoding a peroxisomal membrane protein that functions as an E3 ubiquitin ligase in the peroxisome biogenesis pathway. It contributes to the recycling of the PEX5 receptor, which ferries newly synthesized peroxisomal matrix proteins and imports them into the organelle.

In most eukaryotes, PEX12 forms part of the RING-finger peroxin subcomplex with PEX2 and PEX10 at the peroxisomal membrane. This complex, together with the ubiquitin-conjugating enzyme PEX4, catalyzes the ubiquitination of PEX5, enabling its release into the cytosol for another import cycle and thus maintaining continuous peroxisomal protein import.

Structure-wise, PEX12 is a membrane-associated protein containing a zinc-binding RING finger motif that underlies its E3 ligase activity, along with transmembrane regions that anchor it to the peroxisomal membrane.

Clinical significance is linked to mutations in PEX12, which can cause peroxisome biogenesis disorders, including Zellweger spectrum disorders. Affected individuals often present with elevated very long-chain fatty acids, reduced plasmalogens, and impaired peroxisomal metabolism. Phenotypes range from severe to mild, reflecting varying residual peroxisomal function.

Evolutionarily, PEX12 is conserved across fungi, plants, and animals, with yeast Pex12 serving as a functional homolog in the peroxisome import machinery.