LTBR (lymphotoxin beta receptor) is a TNF receptor superfamily member that functions as a critical regulator of lymphoid organ development and immune responses. Primarily expressed on stromal cells and secondarily inducible on lymphocytes, LTBR binds heterotrimeric lymphotoxin (LTα₁β₂) and LIGHT to activate both canonical and non-canonical NF-κB signaling pathways 1. In stromal cells, LTBR is essential for secondary lymphoid organ (SLO) formation; biallelic LTBR mutations cause lymph node aplasia, splenic hypoplasia, and impaired B cell differentiation through defective stromal-immune cell interactions 2. When ectopically expressed in T cells, LTBR enhances proliferation, cytokine secretion, and resistance to exhaustion through constitutive NF-κB activation 3. In the tumor microenvironment, LTBR agonism promotes high endothelial venule and tertiary lymphoid structure formation, enhancing dendritic cell and T cell infiltration to support anti-tumor immunity 4. Conversely, LTBR signaling on tumor cells and lymphatic endothelial cells mediates regulatory T cell-driven immunosuppression and metastasis via non-canonical NF-κB pathways 5. Therapeutically, LTBR inhibition reduces chr12 inflammation-driven tissue damage in COPD by blocking epithelial NF-κB signaling while promoting WNT-mediated lung regeneration 1.