TDP43 was recently identified as a major disease protein in the ubiquitinated inclusions characteristic of a spectrum of neurodegenerative diseases including both sporadic and familial FTLD, sporadic amyotrophic lateral sclerosis, and familial and sporadic Parkinson’s disease, although the extent to which TDP43 drives pathophysiology is unknown. We have established Drosophila models of TDP43-related neurodegeneration by over-expression of wild type and mutant forms of human TDP43 in several different Drosophila tissues. These reagents will enable elucidation of the role of TDP43 in mediating both frontotemporal dementia and amyotrophic lateral sclerosis using biochemical and cell biological analyses, as well as molecular genetic approaches.