TARDBP and amyotrophic lateral sclerosis: These findings together with our previous reports suggest that both abnormal cytosolic accumulation as well as nuclear loss of functional TDP-43 collectively contributes to the DNA damage/repair imbalance, as observed in ALS/FTD patients, which prompted us to develop a conditional nuclei-cytosolic mislocalization mouse model not involving ectopic TDP-43 but by manipulating the endogenous murine Tdp-43 to better unravel the pathogenic mechanism of human ALS/FTD.