The function of MRGPRX1 (MAS related GPR family member X1, Ensembl gene identifier ENSG00000170255) is as follows. G protein-coupled receptor specifically expressed in sensory neurons of dorsal root ganglion, and which is involved in itch perception and pain transmission (PubMed:11850634, PubMed:20004959, PubMed:26582731, PubMed:33358893, PubMed:36302898, PubMed:37347749, PubMed:37591889, PubMed:39725036). Specifically activated by a variety of enkephalin (PENK) neuropeptides, such as BAM22 and BAM8-22, which induce itch in a histamine-independent manner (PubMed:11850634, PubMed:36302898, PubMed:37591889, PubMed:39725036). Activated by some tick defensins, such as I.persulcatus Def1 and I.ricinus Def2, evoking itch (PubMed:33358893). Also activated by conotoxin CNF-Tx2, inducing itch sensation (PubMed:30243794, PubMed:37591889). Activated by the antimalarial drug chloroquine; however, activation requires concentrations that exceed the chloroquine concentrations observed in plasma of patients undergoing chloroquine treatment (PubMed:20004959). Also activated following cleavage by the dust mite cysteine protease Der p1 (PubMed:28768771). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors, such as adenylate cyclase (PubMed:36302898, PubMed:37591889). MRGPRX1 is both coupled to G(q) and G(i) G proteins: G(q) coupling activates phospholipase C-beta, releasing diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) second messengers, leading to sensitize TRPV1 in pruriceptors, while G(i) coupling mediates inhibition of adenylate cyclase activity (PubMed:23074220, PubMed:36302898, PubMed:37347749, PubMed:37591889). Activation of MRGPRX1 in the peripheral nervous system elicits itch, evoking scratching (PubMed:28223516). MRGPRX1 activation in sensory neurons of the nasal mucosa mediates sneezing responses to irritants or influenza-virus (By similarity). Activation in the central nervous system dampens chronic pain: BAM8-22-binding at the central terminals prevents pain signals passing to spinal cord neurons, attenuating spinal nociceptive transmission (PubMed:28223516). Activation by CXCL17 induces chemotactic movement (PubMed:41167449). {ECO:0000250|UniProtKB:Q8CIP3, ECO:0000269|PubMed:11850634, ECO:0000269|PubMed:20004959, ECO:0000269|PubMed:23074220, ECO:0000269|PubMed:26582731, ECO:0000269|PubMed:28223516, ECO:0000269|PubMed:28768771, ECO:0000269|PubMed:30243794, ECO:0000269|PubMed:33358893, ECO:0000269|PubMed:36302898, ECO:0000269|PubMed:37347749, ECO:0000269|PubMed:37591889, ECO:0000269|PubMed:39725036, ECO:0000269|PubMed:41167449}.