The discoveries that repetitive element (RE) transcripts are elevated in C9-ALS/FTD brains (Prudencio et al., 2017), that TDP-43 binds transposable element (TE) transcripts (Li et al., 2012), and that loss of nuclear TDP-43 is associated with decondensation of REs such as long interspersed nuclear elements (LINEs) and consequent LINE1 retrotransposition (Liu et al., 2019) have provided an additional pathobiological mechanism to consider. The gene discussed is TARDBP; the disease is amyotrophic lateral sclerosis.