Importin-8

Importin-8 (IPO8) is a nuclear transport receptor that mediates the import of proteins into the nucleus by recognizing nuclear localization signals and facilitating translocation through the nuclear pore complex in a Ran-GTP-dependent manner (UniProt: O15397). The protein can function autonomously or in association with importin-beta and transports a diverse array of cargo including signal recognition particle proteins, transcription factors, and microRNA-associated complexes. Its normal cellular role is critical for regulating nucleocytoplasmic transport of regulatory proteins.

IPO8 is associated with VISS syndrome (MIM 619472), an autosomal recessive disorder featuring early-onset aortic aneurysm, motor developmental delay, and connective tissue abnormalities (UniProt: O15397). The molecular basis of disease involvement likely relates to disrupted nuclear import of proteins essential for vascular and connective tissue homeostasis.

In Alzheimer's disease, importin-8 is upregulated in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of 0.41 across analyzed subcellular fractions (Chaparral AD proteomics). This elevation may reflect altered nucleocytoplasmic transport dynamics in AD pathology, potentially affecting import of transcription factors and stress-response proteins involved in neurodegeneration.