Ubiquitin received its name because of its ubiquitous expression in eukaryotic cells. Since its discovery more than 40 years ago, the covalent attachment of ubiquitin to proteins has become well established as a degradative signal. However, more recently it has become clear that protein degradation is only one of many processes regulated by ubiquitylation and it has emerged that this 76 amino acid protein is also crucial for the regulation of numerous cellular processes. For example, ubiquitin is also involved in endocytosis, membrane trafficking, DNA repair, and the regulation of signalling pathways and the cell cycle. In this issue, we conclude our Ubiquitin Minifocus with three articles that provide further insight into the diverse roles of ubiquitylation. E3 ubiquitin ligases are central to the post-translational modification of proteins with ubiquitin and – in a Cell Science at a Glance article (p. 531) – Meredith Metzger, Ventzislava Hristova and Allan Weissman provide an overview of the HECT and RING finger families of E3 ubiqitin ligases and their functions. In the Commentary on page 539, Yelena Kravtsova-Ivantsiv and Aaron Ciechanover highlight the role of additional, ‘noncanonical’ ubiquitin-dependent degradation signals. Finally, the Commentary by Anna Schmuckle and Henning Walczak (p. 549) provides insight into how ubiquitylation affects signalling through NF-κB pathways.