Bours et al. (1994) demonstrated that human RELB, when generated in mammalian cells, formed kappa-B-binding heterodimeric complexes with p50 (NFKB1) or p52 (NFKB2). Homodimeric complexes of RELB did not show DNA-binding activity.NF-kappa-B-inducing kinase (NIK, or MAP3K14) is required for osteoclastogenesis in response to pathologic stimuli. Vaira et al. (2008) found that overexpression of Relb, but not Rela, rescued differentiation of mouse Nik -/- osteoclast precursors, indicating that blockade of the alternative NF-kappa-B pathway, rather than the classical NF-kappa-B pathway, is responsible for the osteoclastogenic defect in the absence of Nik. Using Relb -/- mice, they showed that Relb itself was required for Rankl-induced osteoclastogenesis in vitro and for TNF-induced bone resorption in vivo.