PEX2 encodes a 35-kDa peroxisomal integral membrane protein 1 that functions as a component of a retrotranslocation channel mediating peroxisomal protein recycling. PEX2 assembles with PEX10 and PEX12 to form a channel allowing passage of the PEX5 receptor through the peroxisomal membrane 2. As an E3 ubiquitin-protein ligase, PEX2 monoubiquitinates PEX5 at cysteine-11 during retrotranslocation, signaling receptor extraction into the cytosol for recycling. PEX2 also mediates pexophagy by ubiquitinating peroxisomal proteins during starvation and regulates lipolysis by catalyzing Lys-48-linked polyubiquitination of PNPLA2/ATGL in response to reactive oxygen species 3. This ROS-sensing mechanism couples peroxisomal β-oxidation to lipid droplet homeostasis, with therapeutic implications for non-alcoholic fatty liver disease 4. Loss-of-function PEX2 mutations cause peroxisome biogenesis disorders (PBD), manifesting as Zellweger syndrome and related conditions. PEX2-deficient mice display abnormal neuronal migration, cerebellar defects, accumulation of very long-chain fatty acids, and deficient plasmalogens 5, 6. Allele-specific severity variations correlate with disease phenotype ranging from mild to atypical presentations 7.