Membrane-associated guanylate kinase (MAGUK) family members localize to the plasma membrane and function as molecular scaffolds for the assembly of multi-protein complexes. The MAGUK family includes several mammalian proteins related to the Drosophila tumor suppressor discs-large (dlg) gene product, such as postsynaptic proteins, GKAPs, the tight junction associated proteins (ZO-1–3) and the caspase-associated recruitment domain (CARD) proteins, CARD 6, CARD 8-12 and CARD 14. CARD 6 is a 311 amino acid protein that associates with microtubules and acts as a selective mediator of NF?B activation. CARD 6 is structurally and functionally related to the superfamily of interferon (IFN)-inducible GTPases, a group that comprises host defense proteins which mediate cell-autonomous immunity. RICK, the receptorinteracting protein (RIP)-like interacting caspase-like apoptosis regulatory protein kinase, interacts with CARD 6 and targets it to aggresomes, regions of the cell where protein aggregates collect.