The fact that MALT-1 ubiquitination by TRAF6 is essential for TCR- and BCR-induced activation of NF-κB and evidence that MALT-1 plays an important role in the pathogenesis of several autoimmune diseases (e.g., Multiple Sclerosis; Brüstle et al., 2012; Mc Guire et al., 2013) and lymphomas (e.g., Marginal B zone lymphoma and ABC-DLBCL; Ngo et al., 2006; Vega et al., 2011) suggest that MALT-1 inhibition by A20 plays an important role in the prevention of autoimmunity and lymphomas (Figure 2). This evidence concerns the gene TNFAIP3 and diffuse large B-cell lymphoma.