The SUMO pathway constitutes a ubiquitin-like post-translational modification system, which exerts crucial regulatory functions in protein quality control, maintenance of genome integrity, control of gene expression and regulation of cell cycle progression. SUMO homeostasis is disturbed in disease, including neurodegenerative disease and cancer. We aim to understand basic mechanisms of SUMO signaling and ultimately get insight how deregulation of SUMO homeostasis contributes to human disorders.