An investigation by Yang et al. (2022) reported that low-level overexpression (less than 60% above endogenous levels) of wild-type TDP-43 in transgenic mice lead to a variety of phenotypes resembling ALS, such as neuron loss, muscle denervation, astrogliosis, oligodendrocyte injury, demyelination of the spinal cord, neuroinflammation, progressive weakness and paralysis in mid-life. This evidence concerns the gene TARDBP and amyotrophic lateral sclerosis.