The article "Breaking the K48-Chain: Linking Ubiquitin Beyond Protein Degradation" by Sanim Rahman and Cynthia Wolberger reviews the expanding array of ubiquitin signals and their biological roles. Initially discovered for its role in targeting proteins for proteasomal degradation, ubiquitin has since been found to have non-degradative functions. The authors highlight key milestones in the field, including the discovery of K63-linked polyubiquitin chains and their role in DNA repair, the structural basis of K63 polyubiquitin chain assembly, and the non-degradative functions of histone ubiquitination in transcription and the DNA damage response. They also discuss the discovery of linear ubiquitin chains by the LUBAC complex and unexpected chemical linkages, such as oxyster linkages and phosphoribosyl linkages, which challenge the traditional paradigm of ubiquitin conjugation. The article concludes by emphasizing the evolving understanding of ubiquitin's role in cell biology and its potential for therapeutic applications.The article "Breaking the K48-Chain: Linking Ubiquitin Beyond Protein Degradation" by Sanim Rahman and Cynthia Wolberger reviews the expanding array of ubiquitin signals and their biological roles. Initially discovered for its role in targeting proteins for proteasomal degradation, ubiquitin has since been found to have non-degradative functions. The authors highlight key milestones in the field, including the discovery of K63-linked polyubiquitin chains and their role in DNA repair, the structural basis of K63 polyubiquitin chain assembly, and the non-degradative functions of histone ubiquitination in transcription and the DNA damage response. They also discuss the discovery of linear ubiquitin chains by the LUBAC complex and unexpected chemical linkages, such as oxyster linkages and phosphoribosyl linkages, which challenge the traditional paradigm of ubiquitin conjugation. The article concludes by emphasizing the evolving understanding of ubiquitin's role in cell biology and its potential for therapeutic applications.