The acylated peptide hormone ghrelin impacts a wide range of physiological processes but is most well known for controlling hunger and metabolic regulation. Ghrelin requires a unique posttranslational modification, serine octanoylation, to bind and activate signalling through its cognate GHS-R1a receptor. Ghrelin acylation is catalysed by ghrelin O-acyltransferase (GOAT), a member of the membrane-bound O-acyltransferase (MBOAT) enzyme family. The ghrelin/GOAT/GHS-R1a system is defined by multiple unique aspects within both protein biochemistry and endocrinology. Ghrelin serves as the only substrate for GOAT within the human proteome and, among the multiple hormones involved in energy homeostasis and metabolism such as insulin and leptin, acts as the only known hormone in circulation that directly stimulates appetite and hunger signalling. Advances in GOAT enzymology, structural modelling and inhibitor development have revolutionized our understanding of this enzyme and offered new tools for investigating ghrelin signalling at the molecular and organismal levels. In this review, we briefly summarize the current state of knowledge regarding ghrelin signalling and ghrelin/GOAT enzymology, discuss the GOAT structural model in the context of recently reported MBOAT enzyme superfamily member structures, and highlight the growing complement of GOAT inhibitors that offer options for both ghrelin signalling studies and therapeutic applications.

酰化肽激素 ghrelin 影响广泛的生理过程，但以控制饥饿和代谢调节而闻名。Ghrelin 需要一种独特的翻译后修饰，即丝氨酸辛酰化，以通过其同源 GHS-R1a 受体结合和激活信号传导。Ghrelin 酰化由 ghrelin O-酰基转移酶 (GOAT) 催化，该酶是膜结合O-酰基转移酶 (MBOAT) 酶家族。ghrelin/GOAT/GHS-R1a 系统由蛋白质生物化学和内分泌学中的多个独特方面定义。Ghrelin 是人类蛋白质组中 GOAT 的唯一底物，并且在涉及能量稳态和新陈代谢的多种激素（如胰岛素和瘦素）中，它是循环中唯一已知的直接刺激食欲和饥饿信号的激素。GOAT 酶学、结构建模和抑制剂开发的进展彻底改变了我们对这种酶的理解，并为在分子和有机体水平上研究生长素释放肽信号提供了新工具。在这篇综述中，我们简要总结了有关 ghrelin 信号传导和 ghrelin/GOAT 酶学的知识现状，