The aggregated TDP-43 that is present in ALS and FTD tissue is phosphorylated, ubiquitylated and labelled by ubiquilin-1 and -2 (Deng et al., 2011; Neumann et al., 2006) and sequestosome-1 (SQSTM1 or p62) (Arai et al., 2003), all of which target proteins for degradation. This evidence concerns the gene UBQLN1 and amyotrophic lateral sclerosis.