TARDBP and amyotrophic lateral sclerosis: This is supported by findings in the rNLS8 cytoplasmic TDP-43 (TDP-43∆NLS) doxycycline-inducible mouse model of ALS [264], in which TDP-43 phosphorylation is first detected in the cortex during early disease stages but after the accumulation of insoluble TDP-43 first begins.