We have reached a fascinating point in our research on the ubiquitin system’s function, physiology and roles in disease. The attachment of ubiquitin to a protein in the cytosol was first identified as a means to enable degradation of proteins in the cytosol by the proteasome. It was much later that it was discovered that the ubiquitin system fulfils another crucial cellular function: through the dynamics offered by ubiquitination and subsequent deubiquitination it gives a multitude of signalling pathways the required plasticity to initiate but also to limit their signalling output in an exquisitely controlled manner. Whereas certain signalling-related functions employ ubiquitin’s proteasome-targeting function, e.g. the activation of NF-kB following degradation of I-kB, most signalling-related functions of the ubiquitin system are mediated by different types of ubiquitin chains acting as scaffolds for the recruitment of signalling modules to protein complexes which serve as platforms for the triggering of specific signalling complexes. Rather than discussing mainly structural aspects of the ubiquitin system, this conference is dedicated to the study of functional roles of the ubiquitin system, how it works to ensure normal signal transduction, what are the pathological consequences when it is perturbed and how can we harness our knowledge of the ubiquitin system therapeutically for more efficacious treatment of diseases with high unmet clinical need, including cancer, chronic inflammatory and autoimmune disorders as well as neurodegenerative diseases. Importantly, this conference aims to become the go-to forum at which the most current and up-to-date therapeutic avenues that emerge from the study of the ubiquitin system will be presented and discussed.