DCAF11 is a substrate receptor for the CUL4-DDB1 E3 ubiquitin ligase complex that mediates proteasomal degradation of diverse protein substrates. DCAF11 functions as a component of the CRL4 (Cullin4-RING) E3 ligase, where it directs substrate specificity through protein-protein interactions 1. Mechanistically, DCAF11 recognizes and targets proteins for polyubiquitination, leading to proteasome-mediated degradation 2. Clinically relevant substrates include CENP-A (centromeric protein A), whose phosphorylation-dependent degradation by DCAF11 prevents ectopic localization during the cell cycle 2; p21Cip1, a CDK inhibitor whose degradation regulates cell cycle progression 1; Kap1, whose degradation activates Zscan4-mediated telomere lengthening in embryos and stem cells 3; and Nrf2, where DCAF11 contributes to redox homeostasis regulation 4. DCAF11 is emerging as a therapeutically important E3 ligase for targeted protein degradation approaches. Recent studies demonstrate that small-molecule degraders can recruit DCAF11 to eliminate disease-relevant proteins, including BRD4, showing potent antitumor activity in preclinical models 56. DCAF11 appears particularly suitable for targeted protein degradation due to its promiscuous substrate interactions and high occupancy in E3 ligase complexes 7.