Ran-binding protein 9

RANBP9 (Ran-binding protein 9) is a 729-amino acid scaffolding and adapter protein that couples membrane receptors to intracellular signaling pathways and mediates cell spreading and actin cytoskeleton rearrangement (UniProt: Q96S59). It functions as a core component of the CTLH E3 ubiquitin-protein ligase complex, facilitating proteasomal degradation of transcription factors, and enhances HGF-MET and Ras signaling. RANBP9 also stabilizes the pro-apoptotic TP73 isoform and inhibits kinase activity of DYRK family members.

No disease associations are listed in UniProt curated disease data for this protein. However, RANBP9 demonstrates broad involvement in signal transduction, transcriptional regulation, and protein homeostasis pathways relevant to neuronal function and integrin-mediated cell adhesion.

In Alzheimer's disease, RANBP9 is significantly down-regulated in post-mortem AD brain compared to age-matched controls, with a mean log2 fold-change of −0.66 across subcellular fractions analyzed by quantitative proteomics (Chaparral AD proteomics). This down-regulation suggests potential dysregulation of scaffolding-mediated signaling and cytoskeletal dynamics in AD pathology, though the functional consequence remains to be determined.