NALP proteins include the apoptosis regulator APAF1 (apoptotic protease activating factor 1) and mammalian NOD-LRR proteins and are thought to be involved in inflammation and reproduction. NALP4, also known as PYRIN-containing APAF1-like protein 4, has a C-terminal leucine-rich repeat (LRR) region, an N-terminal Pyrin domain (PYD) followed by a NACHT domain, and a NACHT-associated domain. In transfected 293 cells, NALP4 suppressed NF-κB induction by TNF-α and IL-1β, suggesting NALP4 operates at a point of convergence in these two signaling pathways. NALP4 also suppressed NF-κB induction resulting from overexpression of several adapter proteins and protein kinases involved in these pathways, including TRAF2, TRAF6, RIP, and IRAK2, as well as the IKK-alpha and IKK-beta, suggesting that NALP4 is critical in modulating NF-κB activity.
