Exportin-4

Exportin-4 (XPO4) is a nuclear export receptor that mediates the transport of cargo proteins including EIF5A, SMAD3, and PKM2 from the nucleus to the cytoplasm. The protein binds cooperatively to cargo and active Ran-GTP, docks the resulting complex to nuclear pore complexes via nucleoporin interactions, and facilitates cargo release in the cytoplasm following Ran-GTP hydrolysis (UniProt: Q9C0E2). XPO4 also mediates nuclear import of SOX transcription factors SRY and SOX2, establishing its role as a bidirectional nuclear transport regulator.

XPO4 localizes to the nuclear envelope and cytoplasm, functioning as a key component of the Ran-GTP-dependent nuclear transport pathway. UniProt records no primary disease associations for this protein in its curated disease field.

In Alzheimer's Disease, XPO4 is downregulated in post-mortem AD brain tissue compared to age-matched controls (mean log2FC: −0.99; Chaparral AD proteomics). This reduction was detected in a single subcellular fraction from a TMT-labeled quantitative proteomics study examining four fractions (P2, P3, S2, S3) of human brain tissue. The functional significance of decreased XPO4 expression in AD pathogenesis remains to be elucidated.