We reasoned that a first step to clarify the role of TDP-43 in ALS and FTLD would require a systematic and direct comparative investigation of respective disease-linked variants of TDP-43 [4] on neural integrity in vivo—to alleviate seemingly conflicting conclusions drawn from separate experiments addressing different TDP-43 variants in diverse systems at varying expression levels. The gene discussed is TARDBP; the disease is amyotrophic lateral sclerosis.