Emerging understanding of proteostasis signaling has revealed links to a variety of other diseases, from neurodegenerative, metabolic and cardiovascular to diseases of the immune system and cancer. Given the fundamental role of the PN in proteome maintenance new questions arise: • How is the PN altered in disease? • How does the network respond to drug action, or is it crucially involved in conferring drug sensitivity or resistance? • Do cellular or organismal proteostasis profiles determine drug response, disease susceptibility or progression trajectories? Strategically, our integrative research aims at a systems-level understanding of the structure and regulation of the PN throughout the human diseasome toward improved models, markers and therapeutic strategies of clinical value.