MRGPRX1 is a MAS-related G protein-coupled receptor (GPCR) primarily expressed in dorsal root ganglion (DRG) neurons and is a key receptor for itch perception. It can be activated by various endogenous peptides and exogenous ligands, triggering itch and pain signals through Gi and Gq signaling pathways. The activation of MRGPRX1 not only induces the sensation of itch in peripheral neurons but also inhibits neurotransmitter release in the spinal cord via the Gi1 pathway, alleviating chronic pain. Additionally, the structure and activation mechanism of MRGPRX1 have been elucidated, with its unique ligand-binding pocket and activation process providing a theoretical basis for the development of novel analgesic and antipruritic drugs.