BTNL9 is a butyrophilin-like immunoglobulin superfamily member located on the plasma membrane that functions as an immune checkpoint molecule and tumor suppressor. BTNL9 participates in T cell receptor signaling and regulates cytokine production 1. Mechanistically, BTNL9 suppresses cancer cell proliferation and metastasis through p53-dependent pathways, including p53/CDC25C and p53/GADD45 signaling 2. In normal contexts, BTNL9 downregulation impairs immune infiltration; specifically, low BTNL9 expression correlates with reduced B cell, CD4+ T cell, macrophage, and dendritic cell infiltration 1. Clinically, BTNL9 emerges as a prognostic biomarker across multiple cancers. In lung adenocarcinoma, breast cancer, thyroid cancer, and uveal melanoma, BTNL9 downregulation associates with poor overall survival and unfavorable outcomes 1234. A Polynesian-specific stop-gain variant (rs200884524) in BTNL9 associates with dyslipidemia, indicating metabolic functions 5. Additionally, elevated BTNL9 expression in BRAF-mutated colorectal peritoneal metastases suggests potential therapeutic targeting 6. In idiopathic pulmonary fibrosis, BTNL9 downregulation impairs alveolar protection 7. These findings establish BTNL9 as a multifunctional tumor suppressor and immune modulator with translational potential for cancer diagnosis and therapy.