Cells undergo many important processes to maintain a balanced environmental state as differentiation to repair tissues and degradation of misfolded or unneeded proteins. The ubiquitin system degrades proteins involved in basic biological functions such as cell cycle control and organismal development. When these processes are dysregulated, over-proliferation and defects in tissue regeneration can lead to disease. Ubiquitination occurs through ubiquitin activation by enzyme 1 (E1), attachment by the ubiquitin conjugating protein E2, which then leads to the formation of catalyzing complexes called E3 ubiquitin ligases that target substrates for proteasome destruction or non-proteolytic downstream pathways. There are a vast number of predicted E3 ligases for which cellular roles and protein targeting mechanisms remain unknown.