In summary, Drosophila data from the genetic screen and follow-up studies very closely match our results in mammalian systems, strongly supporting a role for KPNB1/Ketel and other NIRs as protective modifiers of TDP-43 proteinopathy that specifically target pathological TDP-43 across diverse in vitro and in vivo models. This evidence concerns the gene KPNB1 and proteostasis deficiencies.