TARDBP and tauopathy: In addition, nSMase2 deficiency triggers tauopathy, and ataxin-2 deficiency has a specific rescue effect not only for TDP-43 neurotoxicity but also in general on tauopathies [29,118], so the chronic transcriptional downregulation of Smpd3 might be a contributor to the SCA2-specific process of neurodegeneration.