In the attempt to better control TDP-43 levels due to ectopic expression systems (Karim et al., 2013), we here generated novel yeast models that conditionally express human TDP-43 (either WT or bearing ALS-related mutations), from either single or multiple copies of the coding sequence stably integrated in the yeast genome by the CRISPR-Cas9 technique. The gene discussed is TARDBP; the disease is amyotrophic lateral sclerosis.