Psoriasis is an auto-inflammatory disease that affects skin and other organs and leads to the impaired quality of life. Approximately 2 to 3% of the worldwide population suffers from this debilitating condition, the causes of which are currently poorly understood. A gene called CARMA2 has been identified as a psoriasis susceptibility gene. Little is known about the biochemical function and physiological role of the CARMA2 protein. During my first post-doctoral FWO mandate we have shown that the paracaspase MALT1 interacts with CARMA2 in keratinocytes and is indispensable for signaling mediated by CARMA2 and psoriasis-associated CARMA2 mutants. The aim of this project is to further unravel the CARMA2- mediated signaling cascade, identify novel CARMA2-interacting proteins and to characterize the role of CARMA2 in the pathogenesis of psoriasis using CARMA2 knock-out mice and gain-offunction CARMA2 knock-in mice models. Eventually, this should allow us to investigate the potential of therapeutic targeting of the CARMA2/MALT1 pathway in the treatment of psoriasis.