ADGRB3 (adhesion G protein-coupled receptor B3) is an adhesion GPCR primarily expressed in the brain that regulates synaptogenesis and dendritic spine formation through interaction with ELMO1 and RAC1 signaling pathways 1. The receptor also promotes myoblast fusion via ELMO/DOCK1 mechanisms. Beyond its classical neurological functions, ADGRB3 plays unexpected roles in immune regulation and cancer biology. In T cells, ADGRB3 expression is maintained by the NM II-NKX3-2 pathway and modulates filamentous actin organization to control traction force and cytotoxicity against tumors 2. Loss-of-function mutations in ADGRB3 are associated with neurodevelopmental disorders; biallelic ADGRB3 duplications cause intellectual disability, cerebellar atrophy, and behavioral abnormalities 3. ADGRB3-deficient mice exhibit reduced brain and body weights with social interaction deficits 4. In cancer contexts, ADGRB3 alterations correlate with improved immunotherapy outcomes in both extensive-stage small cell lung cancer 5 and advanced biliary duct cancer 6, suggesting therapeutic potential. ADGRB3 expression also impacts overall survival in endometrial cancer 7. These findings establish ADGRB3 as a multifunctional receptor linking synaptic development, immune cell mechanics, and cancer immunotherapy responses.