The expiry date of the proteins in our bodies is determined by the ubiquitin-proteosome degradation system. Selectivity in this system depends on the interaction of ubiquitin-conjugating (or E2) enzymes with protein-ubiquitin E3 ligases. The human genome encodes a variety of these enzymes: 35 E2s and ~500 E3s. NPC researcher Sjoerd van Wijk (UMC Utrecht) has constructed a genome-wide interaction map of all human E3s with most of the RING-E3s (Molecular Systems Biology 5, 295). For this he employed high-throughput yeast two-hybrid screening. As many RING-E3s are involved in human diseases a reliable map will prove a valuable tool to influence the expiry date of pathological proteins.