Gpr39, a member of the ghrelin family of G protein-coupled receptors, is a zinc-responsive receptor [2]. It can sense changes in extracellular Zn2+ and contribute to the regulation of diverse neurovascular and neurologic functions, such as neuronal excitability, vascular tone, and the immune response [2]. It also participates in multiple metabolic, endocrine, and other physiological activities, including inflammation, cardiovascular diseases, and male fertility [3]. Genetically modified rodent models have been crucial for studying its physiological functions [3].

In biliary acute pancreatitis, Gpr39 knockout mice showed significantly reduced AP induced by bile acids, indicating Gpr39 is necessary and sufficient to mediate bile acid (BA) signaling and is involved in biliary AP pathogenesis [1]. In Ang II-induced hypertension, Gpr39 knockout mitigated vascular fibrosis, augmented endothelium-dependent vasodilation, and inhibited endothelial inflammation, oxidative stress, and apoptosis in mice, potentially by downregulating Nlrp3 [4].

In conclusion, Gpr39 is a key regulator in multiple biological processes. Model-based research, especially Gpr39 knockout mouse models, has revealed its important roles in diseases like biliary acute pancreatitis and Ang II-induced hypertension, providing potential therapeutic targets for these diseases.