Inappropriate NF-kB signaling plays an important role in the initiation and progression of different cancers. MALT1 lymphoma and certain Diffuse Large B-cell lymphomas (DLBCL) are associated with genetic abnormalities in CARD11, BCL10 or MALT1, all resulting in constitutive MALT1-mediated NF-kB activation. CARD11, BCL10 and MALT1 are critical components in antigen receptor induced signalling to NF-xB. Recently, we found that MALT1 has proteolytic activity. It is out general aim to further unravel the molecular mechanisms that regulate MALT1-mediated NF-kB activation, with special emphasis on the function and regulation of MALT1 proteolytic activity in vitro and in vivo (using mouse transgenesis). The obtained knowledge will eventually be used to design and initially characterize specific inhibitors of MALT1.