ADGRE5 (CD97) is an adhesion G protein-coupled receptor that plays crucial roles in immune cell function and cancer biology. As a prototypical adhesion GPCR, ADGRE5 exhibits a compact inactive conformation that undergoes significant conformational changes upon activation, creating larger binding cavities for G protein engagement 1. The receptor is involved in leukocyte activation and migration processes, with demonstrated activation by microbial components such as Porphyromonas gingivalis protease gingipain K 2. In cancer contexts, ADGRE5 shows differential expression across multiple tumor types and serves as a prognostic marker, with higher expression associated with worse outcomes in several cancers including glioblastoma, low-grade glioma, and uveal melanoma 3. Mechanistically, ADGRE5 promotes glycolytic metabolism through MAPK pathway activation, dependent on C-terminal phosphorylation and β-arrestin recruitment 4. The receptor also functions in tumor immune microenvironments, mediating cell-cell communication between osteoblastic cells and macrophages through ADGRE5/CD55 signaling 5. Additionally, ADGRE5 has emerged as a potential therapeutic target, with anti-CD97 antibody-drug conjugates showing selective tumor cell killing capabilities 4, and its expression patterns serving as biomarkers for immunotherapy response prediction 6.