The LTβ receptor (LTβR), a member of the TNFR superfamily, functions as an essential element in the organization of lymphoid tissue and initiation of innate and immune defenses. The LTβR is a type 1 transmembrane glycoprotein with four cysteine-rich motifs in the ectodomain involved in binding to ligands, LTa1β2 and LIGHT. LTβ gene maps near TNFRI and CD27 on chromosome 12pl3. LTβR signaling induces NFkB and Jnk/AP-1 transcription factors and activates a slow apoptotic death in certain adenocarcinoma cell lines. The LTβR cytoplasmic tail binds TRAF2, TRAF3, and TRAF5, but not TRAF6 to propagate signaling. Mice deficient in LTβR lack peripheral lymphoid organs and have disorganized splenic microarchitecture, similar to mice deficient in LTa or LT3 genes. LT6R is expressed on stromal tissue and thus receives signals from activated lymphocytes that mediate tissue organization. The LTβR LTa1β2 cytokine system has unique roles, but functions in some cases with TNFRI and II, and HVEM cytokine systems as an integrated network that orchestrates multiple developmental processes and immune responses.