Abstract Inflammasomes play a crucial role in mediating innate and adaptive immunity against a variety of microbes and danger signals. However, regulatory mechanisms controlling inflammasome effector functions, specifically generation of the bioactive IL-1β in macrophages are not well studied. Pyrin-only proteins (POPs) modulate NF-κB signaling and inflammasome activation, thus restricting the magnitude of innate immune and inflammatory responses in humans. POP1 interferes with IKKα/β activation thus limiting NF-κB activity with no known effect on ASC-dependent inflammasomes. POP2, however, limits the transcriptional activity of NF-κB p65/RelA while also down-modulating the assembly of various ASC-dependent inflammasomes. Here we examine a third human POP, POP3, the product of an NLRP pseudogene with ubiquitous and inducible expression. Like POP1 and POP2, POP3 impairs NF-κB-mediated production of pro-inflammatory cytokines, but fails to inhibit ASC-dependent inflammasomes likely due to the absence of specific acidic residues within its first α helix. Despite high homology to POP2, POP3 is translocated to the nucleus in parallel with NF-kB and inhibits the transcriptional activity of nuclear NF-kB. Collectively, POP3 is a resurrected processed-pseudogene that in addition to other POPs likely represents a further level of control for NF-κB-dependent inflammatory responses