Among the members of the inhibitor of apoptosis (IAP) protein family, only Livin and survivin have been reported to have variant forms. We have found a variant form of c-IAP2 through the interaction with the X protein of HBV using the yeast two-hybrid system. In contrast to the wild-type c-IAP2, the variant form has two stretches of sequence in the RING domain that are repeated in the C-terminus that would disrupt the RING domain. We demonstrate that the variant form has an inhibitory effect on TNF-mediated NF-κB activation unlike the wild-type c-IAP2, which increases TNF-mediated NF-κB activation. These results suggest that this variant form has different activities from the wild-type and the RING domain may be involved in the regulation of TNF-induced NF-κB activation.