约20年前，促动力素（PKs）被发现作为能够引起肠道收缩的小肽。如今，它们已被确认为参与多种生理和病理生理途径的血管生成、抗食欲和促炎细胞因子、趋化因子、激素和神经肽。其改变的表达或突变与几种疾病有关，使它们成为一种潜在的生物标志物。它们的G蛋白偶联受体（GPCRs）PKR1和PKR2具有不同的作用，在心血管、代谢和神经疾病以及疼痛和癌症的治疗中可以作为治疗靶点。本文综述和总结了我们对PK家族功能的当前认识，从心脏和大脑的发育到健康和疾病中的稳态调节。最后，本文总结了内源性肽、合成肽以及PKR1和PKR2的选择性配基、受体的非肽正位和变构调节剂在临床疾病模型中的已确认角色。本文重点强调了我们对PKR配基功能的模棱两可的方面和知识缺口，并阐明了未来PK研究的展望。重要性陈述本综述提供了促动力素家族和PK受体的深入视角，其在疾病中可以不依赖其内源性配体而活性，并展现了"固有"活性。它们的非肽配体在多个临床疾病模型中显示出有希望的效果。PKs可能是几种疾病的诊断生物标志物。对促动力素家族及其受体类型在健康和疾病中的作用进行彻底理解，对于开发具有安全性考虑的新治疗策略至关重要。© 2023作者们。本文为开放获取文章，根据创作共用署名非商业许可协议，允许以任何媒介使用、分发和复制，前提是原始作品得到正确引用并且不用于商业目的。

The prokineticins (PKs) were discovered approximately 20 years ago as small peptides inducing gut contractility. Today, they are established as angiogenic, anorectic and proinflammatory cytokines, chemokines, hormones and neuropeptides involved in variety of physiological and pathophysiological pathways. Their altered expression or mutations implicated in several diseases make them a potential biomarker. Their G-protein coupled receptors (GPCRs), PKR1 and PKR2 have divergent roles that can be therapeutic target for treatment of cardiovascular, metabolic, and neural diseases as well as pain and cancer. This article reviews and summarizes our current knowledge of PK family functions from development of heart and brain to regulation of homeostasis in health and diseases. Finally, the review summarizes the established roles of the endogenous peptides, synthetic peptides and the selective ligands of PKR1 and PKR2, and nonpeptide orthostatic and allosteric modulator of the receptors in preclinical disease models. The present review emphasizes the ambiguous aspects and gaps in our knowledge of functions of PKR ligands and elucidates future perspectives for PK research. Significance Statement This review provides an in-depth view of the prokineticin family and PK receptors that can be active without their endogenous ligand and exhibits "constitutive" activity in diseases. Their non- peptide ligands display promising effects in several preclinical disease models. PKs can be the diagnostic biomarker of several diseases. A thorough understanding of the role of prokineticin family and their receptor types in health and diseases is critical to develop novel therapeutic strategies with safety concerns.© 2023 The Authors. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited and is not used for commercial purposes.