BTN1A1 (butyrophilin subfamily 1 member A1) is a multifunctional transmembrane protein with roles in both lactation and immune regulation. In the mammary gland, BTN1A1 functions in milk-fat droplet secretion by binding xanthine oxidoreductase (XOR) through its cytoplasmic PRY/SPRY/B30.2 domain, stabilizing XOR association with the milk fat globule membrane 1. Beyond lactation, BTN1A1 acts as a coinhibitory immune checkpoint that suppresses T-cell activation 2. BTN1A1-expressing cells inhibit CD4 and CD8 T-cell proliferation, T-cell metabolism, and IL-2 and IFN-gamma secretion 2. Importantly, BTN1A1 expression is mutually exclusive with PD-L1 in tumors, as BTN1A1 inhibits JAK/STAT signaling-induced PD-L1 upregulation, suggesting it represents an alternative immune evasion mechanism 3. BTN1A1 shows clinical relevance across multiple cancers: elevated expression correlates with poor prognosis in BRAF-mutated peritoneal colorectal cancer 4, and it was identified as a ferroptosis-related immune checkpoint in breast cancer 5. BTN1A1 also appears mechanistically linked to multiple sclerosis 6 and supports platelet production in vitro 7. Antibody-mediated BTN1A1 blockade suppresses tumor growth in preclinical models, establishing it as a viable immunotherapeutic target for anti-PD-1/PD-L1-refractory cancers 3.