Novel NBS-2, NBS-3, PYRIN-12/NBS-4, and NBS-5 polypeptides, proteins, and nucleic acid molecules are disclosed. In addition to isolated NBS-2, NBS-3, PYRIN-12/NBS-4, and NBS-5 proteins, the invention further provides NBS-2, NBS-3, PYRIN-12/NBS-4, and NBS-5 fusion proteins, antigenic peptides and anti-NBS-2, anti-NBS-3, anti-PYRIN-12/NBS-4, and anti-NBS-5 antibodies. The invention also provides NBS-2, NBS-3, PYRIN-12/NBS-4, and NBS-5 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-2, NBS-3, PYRIN-12/NBS-4, or NBS-5 gene has been introduced or disrupted. Diagnostic, screening and therapeutic methods utilizing compositions of the invention are also provided.