We also do not contend that large IRE1 clusters artificially result from overexpression: IRE1 levels were found to be highly variable across a panel of cancer cell lines (Harnoss et al., 2019; Harnoss et al., 2020) and it is reasonable to suspect that large clusters of endogenous IRE1 do form in cell lines with elevated amounts of IRE1 protein. The gene discussed is ERN1; the disease is cancer.