PEX6 is a core component of the PEX1-PEX6 heterohexameric AAA-ATPase complex essential for peroxisomal protein import and recycling 1. The complex functions as a protein translocase that recognizes monoubiquitinated PEX5 receptor and processively unfolds it through the PEX2-PEX10-PEX12 retrotranslocation channel via ATP hydrolysis, facilitating PEX5 extraction from peroxisomal membranes and release of imported cargo 2. This recycling mechanism is critical for maintaining peroxisomal matrix protein import capacity. PEX6 mutations account for over 60% of peroxisomal biogenesis disorder cases, causing a spectrum of severity from mild Heimler syndrome (sensorineural hearing loss, retinal dystrophy, amelogenesis imperfecta) to severe Zellweger spectrum disorder with neonatal onset hypotonia, neurological impairment, and elevated very-long-chain fatty acids 34. Functionally, missense mutations may impair protein processing rather than complex stability, suggesting distinct therapeutic approaches 5. Gene therapy strategies restoring wild-type PEX6 expression show promise in improving peroxisomal protein import in patient-derived cells 6, though no treatments are currently available for these progressive disorders.