The fourth member of the TRAF protein family (TRAF4) presents several characteristics that distinguish it from the other members of the family. These characteristics concern the primary sequence of the protein, a strong evolutionary conservation, and a tightly regulated physiological expression during development. The subcellular localization of TRAF4 is controversial as it has been detected at the cell membrane, in the cytoplasm and in the nucleus. Using mouse and fly models, it has been established that TRAF4 is a key molecule in diverse ontogenic processes, particularly in the nervous system. However, the molecular mechanisms of action of TRAF4 remain evasive as it was found to interact with diverse types of proteins leading either to pro-apoptotic or anti-apoptotic functions. Finally, few studies implicated TRAF4 in human diseases.