In summary, we observed a strong hTDP-43 overexpression followed by ALS/FTLD pathologies, such as enriched cytoplasmic and insoluble TDP-43, neuroinflammation as revealed by increased astrogliosis and microgliosis, loss of motor neurons in the spinal cord as well as pronounced motor abnormalities in homozygous TAR6/6 mice (Table 1). Here, TARDBP is linked to amyotrophic lateral sclerosis.