We previously identified an interaction between UBE4B and the endosomal membrane protein hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs), and we have demonstrated that the UBE4B-Hrs interaction is critical for appropriate growth factor receptor GFR trafficking and degradation [7, 10, 12], suggesting a previously undiscovered link between GFR trafficking and neuroblastoma pathogenesis. This evidence concerns the gene RAPGEF5 and neuroblastoma.