NLRP12, a member of the Nod-like receptor (NLR) family of proteins, was originally suggested to act as an inflammasome forming component and a modulator of NF-κB signaling. Recent studies revealed that NLRP12 plays anti-inflammatory roles, as NLRP12-deficient mice are more susceptible to chemically induced colitis, and show a more severe infiltration of granulocytes and T cells. The colitis induced in NLRP12-/- mice is associated with increased production of proinflammatory cytokines and activation of both NF-κB and ERK signaling pathways. NLRP12 was reported to attenuate canonical NF-κB signaling by inhibiting IRAK-1 phosphorylation. NLRP12 also down-regulates non-canonical NF-κB signaling through interaction with TRAF3 and the NF-κB inducing kinase NIK.