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Unexpectedly, both ABIN-1-deficient and ABIN-2-deficient mice exhibit only slightly increased or normal NF-κB responses, respectively, possibly reflecting redundant NF-κB inhibitory activities of multiple ABINs [55,56]. Functional ABIN-3 is expressed in humans, but mice only express a truncated and inactive form lacking the crucial ubiquitin-binding domain [57]. As for A20, ABIN-1 also strongly inhibits TNF-induced apoptosis [58], and ABIN-1 deficient mice die embryonically due to TNF-dependent foetal liver apoptosis [56].\nUsing oligonucleotide microarray analysis, ABIN-1 was identified among TNF-induced genes in human synoviocytes, and high levels of ABIN-1 mRNA were detected in RA tissue biopsies, indicating a potential role for ABIN-1, together with A20, in the negative feedback regulation of NF-κB signalling and the pathogenesis of RA [59]. In a recent study, inhibition of TLR responses by immunoreceptor tyrosine-based activation motif (ITAM)-coupled receptors was shown to depend on the expression of the NF-κB inhibitory proteins ABIN-3 and A20. Moreover, this protective effect of the ITAM was strongly suppressed in inflammatory arthritis synovial macrophages [60]. Interestingly, ABIN-1 polymorphisms have been associated with psoriasis and systemic lupus erythematosus in humans [61,62]. A high degree of overlap between systemic lupus erythematosus and RA susceptibility loci might be expected as the two diseases show some clinical overlap in joint involvement, autoantibody production, systemic features and response to treatments such as B-cell depletion (rituximab). It will therefore be interesting to investigate whether SNPs that have been reported to be associated with systemic lupus erythematosus are also associated with 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