The MAS-related genes (also known as MRGPRs) are a complex family of G protein-coupled receptors initially discovered in sensory neurons. Most of them are orphans, which means that they have no known validated endogenous ligands. Although MRGPRs bear great potential as drug targets, notably in itch and nociception, their study has been hampered by the scarcity or absence of potent and selective ligands, especially for the primate-specific MRGPRX subfamily.