Some people harbor deleterious mutations in disease-relevant genes, yet they are completely healthy. How are scientists trying to understand these so-called ‘genetic superheros’? In this Share Your Research talk, Dr. Mohamed El-Brolosy describes his thesis research in the model organism zebrafish. Dr. El-Brolosy found that genetic compensation to deleterious mutations relies on degradation of the mutant mRNA, which triggers upregulation of compensatory genes in a homology-dependent manner. These findings can inform strategies to better understand and treat genetic diseases, many of which have limited therapeutic options.