In support of this hypothesis, wfs1 expression was induced by aging and stressors (Figs 1, 5 and 7 and S5 Fig), and neuronal knockdown of wfs1 rendered neurons vulnerable to oxidative stress-, altered neuronal excitability- or Alzheimer’s associated tauopathy-induced behavioral deficits and neurodegeneration (Figs 5, 6 and 7). Here, WFS1 is linked to tauopathy.