PEX1 encodes a 143-kDa AAA-ATPase that forms a heterohexameric complex with PEX6, essential for peroxisome biogenesis and maintenance 1. The PEX1-PEX6 complex functions as a protein dislocase that extracts monoubiquitinated PEX5 receptor from peroxisomal membranes through the PEX2-PEX10-PEX12 retrotranslocation channel via ATP-dependent mechanical unfolding, enabling PEX5 recycling and peroxisomal matrix protein import 2. This extraction process unfolds PEX5's TPR repeats and releases bound cargo 1. Mutations in PEX1 are the most common cause of peroxisome biogenesis disorders (PBDs), accounting for approximately 65% of cases 3. Disease severity correlates with mutation type: truncating mutations on both alleles cause severe Zellweger syndrome, while missense mutations typically produce milder phenotypes like neonatal adrenoleukodystrophy and infantile Refsum disease 4. Heimler syndrome, caused by biallelic PEX1 mutations including the common G843D variant, represents a less severe form presenting with sensorineural hearing loss, retinal dystrophy, and amelogenesis imperfecta 5. The G843D mutation reduces PEX1 stability and PEX6 binding affinity, leading to proteasomal degradation; protein stabilization strategies show therapeutic potential 2.