We demonstrated that DNAJB5, which exhibited one of the highest fold increases in abundance in our proteomics dataset at disease onset, co-localized with TDP-43 inclusions in rNLS8 mice and in human post-mortem ALS motor cortex and had potent anti-aggregation effects against cytoplasmic TDP-43 variants. Here, TARDBP is linked to amyotrophic lateral sclerosis.