Thus, the major role of the ALS-associated hTDP-43 mutations appears to be the enhancement of the steady-state level of hTDP-43 through stabilization of the polypeptide in the spinal motor neurons, which have a low tolerance to the elevated cellular level of TDP-43 in comparison to the non-motor neuron cells. This evidence concerns the gene TARDBP and amyotrophic lateral sclerosis.