Novel NBS-1 or PYRIN-1 polypeptides, proteins, and nucleic acid molecules are disclosed. In addition to isolated NBS-1 or PYRIN-1 proteins, the invention further provides NBS-1 or PYRIN-1 fusion proteins, antigenic peptides and anti-NBS-1 or anti-PYRIN-1 antibodies. The invention also provides NBS-1 or PYRIN-1 nucleic acid molecules, recombinant expression vectors containing a nucleic acid molecule of the invention, host cells into which the expression vectors have been introduced and non-human transgenic animals in which a NBS-1 or PYRIN-1 gene has been introduced or disrupted. Diagnostic, screening and therapeutic methods utilizing compositions of the invention are also provided.