GPR132, also known as G2A, is a proton-sensing G protein-coupled receptor that functions as a cellular sensor of acidification and lactate 1. The receptor serves as a key mediator of tumor-macrophage interactions, where it senses rising lactate levels in acidic tumor environments to promote M2 macrophage polarization 2. This lactate-GPR132 signaling facilitates breast cancer metastasis by enhancing cancer cell adhesion, migration, and invasion, with clinical data showing positive correlations between GPR132 expression and poor prognosis 2. In atherosclerosis, lactate-activated GPR132 promotes macrophage senescence through Src phosphorylation, accelerating diabetic atherosclerosis progression 3. The receptor also regulates tissue repair through efferocytosis-induced macrophage proliferation, where lactate signaling via GPR132 stabilizes Myc protein to enable pro-resolving macrophage proliferation 4. Additionally, GPR132 functions as an immune checkpoint regulator in NK cells, inhibiting their cytotoxic function through the Gαs/CSK/ZAP70/NF-κB pathway 5. GPR132 has emerged as a promising therapeutic target for neuropathic pain, cancer, and inflammatory conditions, with potent selective agonists being developed for research applications 67.