For TPD employing bifunctional PROTACs currently only a few of the more than 600 E3 ligases in mammalian cells have been investigated, and mostly the von Hippel-Lindau (VHL)-and Cereblon (CRBN) proteins have been targeted . However, chronic treatment with PROTACs based on VHL and CRBN has given rise to inactivating mutations in the E3 ligases leading to resistance . Also, induction of target degradation may vary among ligases, which may be linked to expression levels of ligases in different tissues or cell types, their particular subcellular localization, or different structural matches in the interaction interfaces formed between ligases and targets. Therefore, the discovery of new E3 ligases, which may offer novel opportunities for drug discovery, is in high demand but in short supply. The findings reported here together with the results of Cravatt et al. suggest that DCAF11 may be a very suitable candidate ligase worth exploring for chemical biology and medicinal chemistry and drug discovery programs in a broader sense.