The FN14 (TNFRSF12A) intracellular domain lacks the characteristic death domain of TNF receptor superfamily (TNFRSF) but contains TNFR-associated factor (TRAF) binding sites. Upon TWEAK binding, FN14 recruits TRAF2 and TRAF3 to activate both canonical and non-canonical nuclear factor-kappa B (NF-kB) pathway (Brown et al. 2003, Saitoh et al. 2003, Sanz et al. 2010). NF-kB activation plays a key role in TWEAK-elicited inflammatory responses. TWEAK/FN14 binding induces NIK activation through targeting the degradation of TRAF2/cellular inhibitor of apoptosis (cIAP) 1 and 2 complex (Vince et al. 2008). TWEAK activation of the non-canonical NF-kB pathways promotes inflammatory responses in tubular cells. In cultured renal tubular cells TWEAK increases nuclear RelB/p52 accumulation, RelB and p52 DNA-binding activity, and NIK- and RelB-dependent CCL21 and CCL19 expression (Poveda et al. 2010).