Lymphotoxin beta (LTB) is a cytokine that binds to the LTBR/TNFRSF3 receptor 1 and serves as a membrane anchor for heterotrimeric complex attachment to the cell surface. LTB plays a critical role in immune response regulation through multiple mechanisms. It positively regulates NF-kappaB signal transduction and extrinsic apoptotic signaling [GO annotations], contributing to dendritic cell homeostasis and regulation of necroptotic processes. LTB is involved in cytokine signaling cascades, including positive regulation of interleukin-12 production and type I interferon regulation [GO annotations]. The gene's clinical significance is highlighted in immune-mediated inflammatory diseases (IMIDs) such as rheumatoid arthritis and inflammatory bowel disease. TNF inhibitors and JAK inhibitors, which impact lymphoid signaling pathways related to LTB function, carry the highest risk of tuberculosis reactivation in patients with latent tuberculosis infection 2. In rheumatoid arthritis specifically, blocking upstream biological agents like TNF-α and IL-6 has improved disease outcomes, though some patients remain treatment-refractory 3. The LTB signaling pathway represents a potential therapeutic target for inflammatory diseases, though isoform 2 is likely non-functional [UniProt annotation].