The VHL/Cul2 E3 ubiquitin ligase complex ubiquitinates the 35-kDa CTF TDP-43 in vitro, colocalizes with TDP-43 inclusions in HEK293A and in ALS patient oligodendrocytes, and facilitates proteasomal-dependent turnover of CTFs in vivo based on genetic studies (Uchida et al., 2016). This evidence concerns the gene TARDBP and amyotrophic lateral sclerosis.