The finding that most, if not all, TDP-43 aggregates are amorphous in the spinal cord and brain of ALS and FTLD-U patients, in bacterial IBs and finally in aggregates formed in vitro from purified TDP-43, suggests that this protein has an intrinsic propensity to form amorphous aggregates and that such a propensity is not affected remarkably by specific factors present in the biological compartments where aggregation occurs. This evidence concerns the gene TARDBP and amyotrophic lateral sclerosis.