Peroxisomal membrane protein PEX14

PEX14 is a peroxisomal membrane protein that functions as a component of the PEX13-PEX14 docking complex, a translocon channel mediating the import of peroxisomal cargo proteins bound to the PEX5 receptor (UniProt: O75381). The complex forms a large import pore approximately 9 nm in diameter through which cargo proteins translocate into the peroxisome matrix. PEX14 also plays a role in peroxisome movement through direct interaction with tubulin.

Mutations in PEX14 cause peroxisomal biogenesis disorders, including Peroxisome Biogenesis Disorder 13A (PBD13A), a fatal condition characterized by severe neurologic dysfunction, psychomotor retardation, hypotonia, neonatal seizures, and multiple systemic abnormalities (UniProt: O75381). These disorders result from failure of protein import into peroxisomes, leading to the absence of functional organelles.

PEX14 is downregulated in Alzheimer's disease brain tissue compared to age-matched controls, with a mean log2 fold-change of −0.44 (Chaparral AD proteomics). This reduction in peroxisomal import capacity may reflect impaired cellular stress responses and metabolic dysfunction characteristic of AD neuropathology.