CNR2 is a G protein-coupled receptor that binds endocannabinoid ligands and mediates inhibition of adenylate cyclase 1. The receptor is expressed across diverse tissues including testis, brain, spleen, and peripheral immune tissues, with tissue-specific isoforms (CB2A and CB2B) showing differential expression patterns 2. In immune cells, CNR2 suppresses T-cell antitumor responses by binding JAK1 and inhibiting downstream STAT signaling, thereby impairing cannabinoid-mediated anticancer immunity 3. In skin keratinocytes, CNR2 activation suppresses adenylate cyclase 3, reducing cAMP and Epac1 activation to limit IL-33 production and thereby alleviate atopic dermatitis pathology including itch and inflammation 1. CNR2 also functions as a metabolic gatekeeper in B-lymphoid cells, restricting glucose and energy supply to prevent malignant transformation 4. The CNR2 gene polymorphism rs2501432 is significantly associated with depression susceptibility 5, and rs2229579 variants correlate with synthetic cannabinoid use disorder 6. CNR2 pharmacogenetics influence individual responses to cannabinoid therapeutics and may guide personalized medicine approaches 7.