Analogous to UBE4B [37], reduced expression of the gene for the HECT family E3 ubiquitin protein ligase ITCH (also called Atrophin-1-interacting protein 4 (AIP4); Fig. 2A) is associated with stage 4 disease, MYCN amplification, and poor neuroblastoma patient outcomes (Supplemental Fig. 1). This evidence concerns the gene ITCH and neuroblastoma.