Mas-related G protein-coupled receptors (GPCRs) of subfamily X, designated MRGPRX, are primate-specific orphan receptors that belong to the δ-branch of rhodopsin-like, class A GPCRs. Four distinct subtypes exist, MRGPRX1, -2, -3, and -4, MRGPRX2 having the lowest degree of similarity with the others. Due to their expression on sensory neurons and immune cells, and their roles in pain perception and transmission, itch, inflammation, immune defense, pseudo-allergic reactions, wound healing, and possibly cancer, they have recently attracted much attention as novel drug targets. In particular MRGPRX2 was identified as an important mast cell receptor responsible for anaphylactoid drug reactions, and involved in skin and mucosal diseases, e.g. urticaria, atopic dermatitis, rosacea, and allergic rhinitis. A major hurdle has been the lack of animal models for studying these primate-specific receptors. However, recently humanized mice have been created. Moreover, a mouse ortholog of MRGPRX2, MRGPRB2, was identified, both receptors having a certain degree of similarity. MRGPRX1 and -2 can be activated by various peptides and small (partly peptidomimetic) molecules. MRGPRX2 is additionally activated by a very broad range of basic molecules, positively charged at physiologic pH value of 7.4, including many drugs. MRGPRX4 is activated by small acidic molecules including bile acids. For MRGPRX3, no ligands have been reported yet. Antagonists with reasonable potency and selectivity have been described for MRGPRX1, and few antagonists also for MRGPRX2, but not for the other subtypes. The recent elucidation of cryogenic electron microscopy structures of MRGPRX2 and -4 is expected to facilitate and advance drug development for these receptors. Currently, research on MRGPRX is still in its infancy, and exciting discoveries can be awaited. These receptors have great potential as future drug targets.

X 亚科的 Mas 相关 G 蛋白偶联受体 (GPCR)，称为 MRGPRX，是灵长类动物特异性孤儿受体，属于视紫红质样 A 类 GPCR 的 δ 支。存在四种不同的亚型，MRGPRX1、-2、-3 和-4，MRGPRX2 与其他亚型的相似度最低。由于它们在感觉神经元和免疫细胞上的表达，以及它们在疼痛感知和传递、瘙痒、炎症、免疫防御、假性过敏反应、伤口愈合以及可能的癌症中的作用，它们最近作为新的药物靶点引起了很多关注。具体而言，MRGPRX2被鉴定为负责类过敏药物反应的重要肥大细胞受体，并且涉及皮肤和粘膜疾病，例如荨麻疹、特应性皮炎、红斑痤疮和过敏性鼻炎。一个主要障碍是缺乏研究这些灵长类动物特异性受体的动物模型。然而，最近已经创造了人源化小鼠。此外，鉴定了MRGPRX2的小鼠直系同源物MRGPRB2，两种受体具有一定程度的相似性。MRGPRX1 和 -2 可以被各种肽和小（部分肽模拟物）分子激活。MRGPRX2 还被非常广泛的碱性分子激活，在生理 pH 值为 7.4 时带正电，包括许多药物。MRGPRX4 被包括胆汁酸在内的酸性小分子激活。对于 MRGPRX3，尚未报告任何配体。已经描述了 MRGPRX1 具有合理效力和选择性的拮抗剂，很少有 MRGPRX2 拮抗剂，但其他亚型没有。最近对 MRGPRX2 和 -4 的低温电子显微镜结构的阐明有望促进和推进这些受体的药物开发。目前，MRGPRX 的研究还处于起步阶段，等待着令人兴奋的发现。这些受体具有作为未来药物靶点的巨大潜力。