MRGPRX3 is a primate-specific orphan G protein-coupled receptor belonging to the rhodopsin-like class A GPCR family 1. As a member of the MAS-related GPCPRX subfamily, MRGPRX3 is expressed on sensory neurons and likely plays a role in nociceptor function and pain modulation, though its specific endogenous ligands remain unidentified 1. MRGPRX3 is constitutively expressed in human keratinocytes, where it mediates cellular responses to antimicrobial peptides including cytokine/chemokine production, cell migration, and proliferation through MAPK and NF-κB signaling pathways 2. MRGPRX3 has been identified as a molecular marker for corneal endothelial cells, suggesting tissue-specific expression patterns 3. Clinically, MRGPRX3 is implicated in pain-related pathologies; it was identified among genes involved in abdominal pain transmission in irritable bowel syndrome patients 4, and genetic variants near MRGPRX3 show sex-specific associations with hallux valgus, suggesting roles in inflammation and skeletal development 5. Transgenic rat models overexpressing human MRGPRX3 exhibit abnormal skin phenotypes and cataracts, indicating that dysregulated expression disrupts normal cell differentiation 6. MRGPRX3 expression is reduced following electronic cigarette exposure via miRNA regulation 7, highlighting environmental sensitivity.