The MDM4 gene encodes a nuclear protein that contains a p53 binding domain at the N-terminus and a RING finger domain at the C-terminus, and shows structural similarity to p53-binding protein MDM2. Both proteins bind the p53 tumor suppressor protein and inhibit its activity, and have been shown to be overexpressed in a variety of human cancers. However, unlike MDM2 which degrades p53, this protein inhibits p53 by binding its transcriptional activation domain. The p53 inhibitor MDM4 is present at high levels in multiple human cancers. MDM4 upregulation in malignancies is mostly ascribed to MDM4 gene amplification. Gene amplification and consequent upregulation of MDM4 are reported in multiple types of human tumors including glioma, soft tissue sarcoma, head and neck squamous carcinoma, retinoblastoma, melanoma, and breast cancer.