The Ubiquitin Proteasome System (UPS) controls a majority of the principal functions of almost all the cellular proteins of human cells. Failures in this system often contribute directly or indirectly to the pathogenesis of many diseases, including cancer, inflammation, and neurodegeneration. There are ~700 E3 ubiquitin ligases encoded in human genome and the functions of most of these E3s remain unknown. Recent development of PROTAC drugs to recruit E3 ligases and degrade therapeutic proteins highlight the value of studying E3 ligases. Substrate identification in individual E3 ligases is an essential step to unraveling cellular functions of E3s and identifying novel therapeutic targets. Lifesensors can help you identify the substrates of your preferred E3s.