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The tumor necrosis factor receptor-associated factor (TRAF) family, consisting of seven members (TRAF1-7), is a group of signaling adaptors which participate in various signaling pathways through binding of the tumor necrosis factor receptor superfamily. As one of the important member of TRAF family proteins, TRAF4 was initially isolated from breast carcinomas and identified as the first member of the TRAF family to be up-regulated in human carcinomas. TRAF4 is required during embryogenesis in key biological processes including the formation of the trachea, the development of the axial skeleton, and the closure of the neural tube. TRAF4 deficiency leads to severe developmental alterations.