Tumor necrosis factor‐α (TNF‐α) induces the transcriptional activation of numerous genes involved in the inflammatory response. The recently identified protein TRUSS was investigated for its role in TNF‐α‐induced activation of c‐Jun‐NH2 terminal kinase (JNK) and transcription factor, AP‐1. Ectopic expression of TRUSS activated JNK and AP‐1 in the absence and presence of TNF‐α stimulation. The C‐terminal region of TRUSS interacted with TNF receptor‐associated factor‐2 (TRAF2) and co‐expression of dominant‐inhibitory TRAF2 with TRUSS inhibited AP‐1 activation, suggesting that TRUSS signaling occurs upstream of TRAF2. Further, a dominant‐inhibitory mutant of TRUSS inhibited TNF‐α‐induced AP‐1 activation. These findings suggest that TRUSS activates JNK in a TRAF2‐dependent fashion and is involved in TNF‐α‐induced AP‐1 activation via JNK kinases.