BTN3A1 (butyrophilin subfamily 3 member A1) is a transmembrane protein that plays critical roles in both γδ and αβ T cell regulation. For γδ T cells, BTN3A1 cooperates with BTN2A1 to form a phosphoantigen-sensing complex, where phosphoantigens such as HMBPP function as 'molecular glues' to promote heteromeric association between their intracellular domains 1. This phosphoantigen-mediated interaction drives conformational changes that enable γδ T cell receptor activation through a 'plier-like gripping' mechanism 2. BTN3A1 expression is regulated by metabolic stress through AMPK-dependent pathways, with ATP-producing processes and metabolic crises altering BTN3A1 cell surface levels 3. In αβ T cells, BTN3A1 acts as an immune checkpoint molecule by inhibiting T cell receptor activation through preventing segregation of N-glycosylated CD45 from the immune synapse 4. Disease associations include roles in cancer immunosurveillance, where BTN3A1-targeting antibodies can coordinate both αβ and γδ T cell antitumor responses 4, and autoimmune disorders like systemic lupus erythematosus, where BTN3A1 polymorphisms influence disease susceptibility 5. These dual regulatory functions position BTN3A1 as a potential therapeutic target for cancer immunotherapy and autoimmune disease treatment 6.