BTN3A2 (butyrophilin subfamily 3 member A2) is a transmembrane immunoregulatory protein that plays multifaceted roles in T cell activation and disease pathogenesis. Primary Function: BTN3A2 functions as a co-receptor for γδ T cell activation, operating within multimeric butyrophilin complexes. Structurally, BTN3A2 interacts extracellularly with BTN2A1 and intracellularly via its B30.2 domain with BTN3A1 to form phosphoantigen-sensing receptor complexes 12. Mechanism: The protein exhibits a "plier-like gripping" mechanism where BTN multimers bridge TCR surfaces to drive γδ T cell activation upon phosphoantigen recognition 1. BTN3A2 undergoes ligand-induced inside-out stabilization, enhancing complex stability and TCR activation efficiency 2. Disease Relevance: BTN3A2 is implicated in depression susceptibility 3, chr6 kidney disease 4, rheumatoid arthritis with comorbid depression 5, and preeclampsia 6. In preeclampsia, BTN3A2 interacts with MFGE8 to promote ferroptosis and inhibit angiogenesis 6. Clinical Significance: BTN3A2 is identified as a potential diagnostic biomarker and therapeutic target across multiple conditions, particularly for immunotherapies targeting γδ T cells distinct from conventional αβ T cell approaches 1, and for treating placental vascular disorders in preeclampsia.