PEX6

PEX6 is a gene that encodes peroxisomal biogenesis factor 6, a member of the AAA-ATPase family. The PEX6 protein participates in the peroxisomal matrix protein import machinery by forming a complex with PEX1. This ATPase complex associates with the peroxisomal membrane via the docking factor PEX26 and uses ATP hydrolysis to extract receptor-cargo complexes, such as PEX5 and PEX7, from the membrane after delivery of their cargo. This activity enables repeated rounds of import of peroxisomal proteins and is essential for the maintenance and function of peroxisomes.

Disruption of PEX6 impairs peroxisome biogenesis and leads to peroxisomal biogenesis disorders (PBDs) in humans, most prominently within the Zellweger spectrum. The clinical presentation varies from severe neonatal Zellweger syndrome to milder infantile Refsum-type disease. Biochemical features typically include elevations of very long-chain fatty acids in plasma, reductions in plasmalogens, and other abnormalities reflecting impaired peroxisomal beta-oxidation and lipid metabolism. Common clinical manifestations include hypotonia, developmental delay, craniofacial dysmorphisms, hepatomegaly, and sensory deficits, though the severity is variable.

Inheritance of PEX6-related disorders is generally autosomal recessive. Diagnosis combines genetic testing to identify pathogenic variants in PEX6 with biochemical assays indicating peroxisomal dysfunction. Management is supportive and multidisciplinary, focusing on addressing metabolic abnormalities and associated organ-system complications. Ongoing research uses cellular and animal models to better understand PEX6 function, peroxisome biogenesis, and potential therapeutic approaches.