Prion proteins are infamous for going rogue. In the brain, misfolded versions of the proteins can convert normally folded prions into forms that cause neurodegenerative diseases such as mad cow disease and fatal familial insomnia. But researchers know little about the everyday function of prions. A team of scientists now report that the proteins bind to a specific cell receptor to help maintain the electrical insulation on nerve cells outside of the brain (Nature 2016, DOI: 10.1038/nature19312). In 2010, Adriano Aguzzi of the University of Zurich and colleagues reported that mice engineered to lack the prion protein gene lost this lipid-and-protein coating, which is called myelin. Now, through a series of experiments, Aguzzi’s team demonstrates that a 28-amino-acid sequence on one end of the prion protein binds to and activates a receptor called Gpr126 on Schwann cells, which are responsible for maintaining myelin sheaths. Once activated, these receptors trigger cellular signaling critical for the myelination process. When the scientists deleted the gene for the receptor from cultured Schwann cells, the prion protein no longer activated this signaling. These findings still don’t explain what prion proteins do inside the brain because Schwann cells are present only in the peripheral nervous system. Aguzzi says his team is actively looking for a brain receptor that binds the prion protein.