•optoTDP-43 accumulations are similar to TDP-43 accumulations in TDP-43 proteinopathy.•RNA-FISH performed on ALSs' spinal cord and FTLDs' brain with a poly-T probe and failed to found TDP-43/mRNA colocalization. TDP-43 inclusions lacked mRNA.•No colocalization between TDP-43 and G3BP1/ATKN2 inclusions was detected. The gene discussed is TARDBP; the disease is proteostasis deficiencies.