Gpr132, also known as G2A, is a proton-sensing G-protein coupled receptor. It plays crucial roles in various biological processes, being involved in sensing acidification and lipid-transmembrane receptor signalling. It has been associated with pathways related to immune cell regulation, cell differentiation, and tumour-macrophage interplay, which are of great biological importance. Genetic models, such as gene knockout (KO) mouse models, have been instrumental in studying its functions [3].

In breast cancer, Gpr132 deletion reduces M2 macrophages and impedes lung metastasis in mice, indicating its role in promoting breast cancer metastasis by mediating tumour-macrophage interplay through sensing lactate [1]. In type 2 diabetes, GPR132 deficiency in macrophages reverses metabolic disorders in high-fat diet-fed mice, highlighting its contribution to islet macrophage reprogramming [2]. In NK cell function regulation, GPR132-/-mice have a higher proportion of mature NK cells with stronger anti-melanoma capabilities, and GPR132-deficient NK92 cells show enhanced cytotoxicity. GPR132 regulates NK cell function through the CSK/ZAP70/NF-κB signaling axis [4].

In conclusion, Gpr132 is a multifunctional receptor involved in immune cell regulation, cell differentiation, and tumour-related processes. Studies using KO mouse models have revealed its significant roles in breast cancer metastasis, type 2 diabetes, and NK cell-mediated anti-tumour functions, providing insights into potential therapeutic targets for these diseases.