Paralogous proteins have evolved from gene or whole genome duplications and may provide an insurance policy for deleterious mutations. Why some paralogous proteins exist, however, remains somewhat enigmatic, as they consume substantial cellular energy resources despite often having homologous functions. In a new study published in Nature Communications, corresponding author Dea Slade, together with first author Johannes Benedum and their team, investigated the paralogous proteins PHD finger protein 3 (PHF3) and Death-inducer obliterator (DIDO). They found that the proteins collaboratively regulate gene expression and that, intriguingly, transcriptional upregulation of DIDO3 can compensate for the loss of PHF3. Collaborators are the Zagrovic lab and the Akalin lab at the Berlin Institute for Medical Systems Biology.