The NIID intranuclear inclusions are immunoreactive for ubiquitin, p62/SQSTM1, SUMO1, FUS, and OPTN, suggesting that nuclear ubiquitin-mediated proteasome pathways are normally functioning in the nucleus and those pathways are aberrantly stimulated in NIID (Pountney et al., 2003; Franic et al., 2021). This evidence concerns the gene OPTN and neuronal intranuclear inclusion disease.