Frontotemporal dementias and amyotrophic lateral sclerosis are fatal neurodegenerative diseases which share the formation of abnormal protein clumps (inclusions) in nerve cells composed of the protein TDP-43. While the exact mechanisms on how TDP-43 inclusions are formed and how this leads to cell death are so far only incompletely understood, it is evident that TDP-43 plays a major role in the pathogenesis of these diseases. In the disease process, TDP-43 becames abnormally phosphorylated, This process is regulated by enzymes called kinases which add a phosphate group to an amino acid in the protein. Abnormal phosphorylation of TDP-43 might interfere with the normal function of TDP-43 or increase the aggregation tendency of this protein Therefore, the aim of this proposal is to identify specific kinases which modulate the phosphorylation state of TDP-43 in a cell culture assay. Identified kinases might act as new drug targets and open new therapeutic approaches in FTD and ALS research.