Peroxisomal ATPase PEX1

PEX1 (Peroxisomal ATPase PEX1) is an AAA ATPase that functions as a core component of the PEX1-PEX6 protein dislocase complex (UniProt: O43933). It catalyzes ATP-dependent extraction of the monoubiquitinated PEX5 receptor from peroxisomal membranes, enabling PEX5 recycling and release of imported cargo—an essential step in peroxisomal protein homeostasis.

PEX1 is primarily expressed in cells with active peroxisomal biogenesis and protein import. Mutations in PEX1 cause a spectrum of peroxisome biogenesis disorders, ranging from severe neonatal conditions such as Zellweger syndrome (PBD1A, MIM 214100) and neonatal adrenoleukodystrophy (PBD1B, MIM 601539) to milder forms like Heimler syndrome (HMLR1, MIM 234580), all characterized by neurological, hepatic, and sensory deficits (UniProt: O43933).

PEX1 is downregulated in Alzheimer's disease brain tissue. Analysis of post-mortem AD brain versus age-matched controls using TMT-labeled proteomics across four subcellular fractions revealed a mean log2 fold-change of −0.39 (Chaparral AD proteomics). This downregulation suggests impaired peroxisomal protein import capacity in AD pathology, potentially affecting lipid metabolism and oxidative stress responses critical to neurodegeneration.