PEX12 is a peroxisomal membrane protein essential for peroxisome biogenesis and organization. It functions as a component of a retrotranslocation channel composed of PEX2, PEX10, and PEX12, where each subunit contributes five transmembrane segments that coassemble into an open channel 1. PEX12 contains a zinc-binding RING finger domain at its C-terminus 2 and mediates recycling of the PEX5 import receptor from peroxisomes to the cytosol 3. The protein interacts directly with both PEX5 and PEX10 through its zinc-binding domain 2, and regulates PEX5 recycling by activating the E3 ubiquitin ligase activity of PEX10. When recycling is compromised, PEX12 stimulates polyubiquitination of PEX5, leading to its degradation 1. PEX12 is essential for peroxisomal matrix protein import 4 and plays a critical role in plant and mammalian development 5. Mutations in PEX12 cause peroxisome biogenesis disorder complementation group 3, including Zellweger syndrome, a lethal neurological disorder characterized by defective peroxisomal protein import 46. Genotype-phenotype correlation suggests that loss of PEX12 function produces more severe clinical phenotypes 7.