PDZ domains are abundant protein and lipid recognizing modules that function as central organizers and regulators of dynamic cell signaling processes. In conjunction with cell membrane proteins, proteins comprising PDZ domains facilitate transmission of extracellular information into physiological output. PDZnet has been an ambitious PhD training network that brought together cutting-edge life sciences disciplines, ranging from chemical synthesis of PDZ domain modulators to studies in live animals with the overarching aim of gaining fundamental insight into the role of the PDZ interactome in cell biology and human physiology. PDZnet conducted basic research that advanced our understanding of how PDZ domain proteins act as cellular motherboards that orchestrate signaling pathways, including recognition, differentiation and integration of extracellular stimuli into appropriate cellular responses. The PDZnet research thereby aimed to shed light on the molecular machinery that is fundamental to life. While the immediate translational perspectives of a project like PDZnet can be challenging to grasp, the insights obtained from our work might in fact pave the way for advancing the utilization of PDZ domains as relevant therapeutic intervention points in major age- associated pathological conditions including cancer, stroke and Alzheimer’s disease. Despite recent intensive drug development efforts, poor treatment opportunities remain a common denominator for these rapidly growing diseases. By bringing together leading academic and industrial experts, PDZnet has enhanced the awareness of PDZ domains as novel therapeutic targets and may stipulate a paradigm-shift in industrial drug discovery programs. Potential drug candidates ascending from the PDZnet research will benefit the aging European population and the European economy, which is overburdened by increasing healthcare costs. Finally, each of the individual 14 PhD fellows will benefit from a highly structured, innovative and interdisciplinary training that has enhanced their future career perspectives and their contribution to progressing human knowledge.