During muscle atrophy, contractile proteins are degraded by proteolytic systems, such as the ubiquitin-proteasome system. Although previous studies have implicated the ubiquitin ligase MuRF1 in the degradation of muscle proteins, relatively little is known about other proteins that aid MuRF1 in this function. Jens Fielitz, Thomas Sommer and colleagues (Nowak, Suenkel et al., 2019) now employ a yeast two-hybrid and proteomic screen to identify MuRF1 co-factors. They show that MuRF1 binds DCAF8, a substrate receptor in the Cul4-containing ring ubiquitin ligase complex (CRL4) complex, and find that these two proteins partially colocalise in muscle cells. MuRF1 also interacts with DDB1, a further component of CRL4, indicating that MuRF1 binds DDB1 and DCAF8 in the context of the CRL4 complex. Interestingly, DCAF8 expression mimics that of MuRF1 during muscle atrophy as both proteins become upregulated in de-nervated muscles. The authors demonstrate that DCAF8, like MuRF1, is required for degradation of myosin heavy chains (MyHCs) and for the induction of shrinkage in cultured myotubes upon artificial atrophy. Taken together, these findings suggest that DCAF8 and MuRF1 cooperate with CRL4 ubiquitin ligases to target proteins, such as MyHCs, for degradation during muscle atrophy.