The loss of cellular homeostasis often leads to the activation of the endoplasmic reticulum (ER) stress-triggered unfolded protein response (UPR) pathway and the impairment of the nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway, which play vital roles in ND pathogenesis (Branca et al., 2017; Ren et al., 2021). The gene discussed is NFE2L2; the disease is Norrie disease.