Abstract: Polyubiquitin chains linked through different lysines of ubiquitin may exert both proteasome-dependent and -independent functions. In a recent Cell issue, Xu et al. employ quantitative proteomics to profile polyubiquitin linkages in yeast. They find that linkages through all lysines of ubiquitin, except lysine-63, can target proteasomal degradation in vivo, and that lysine-11 polyubiquitination is important for endoplasmic reticulum-associated degradation (ERAD).