SKIC2 and cirrhosis of liver: Mutations in SKIV2L cause THES, characterized by chronic diarrhea, liver disease, hair abnormalities, and high mortality in early childhood due to severe infection or liver cirrhosis.157, 158 It has been shown that the unfolded protein response (UPR), which generates endogenous RLR ligands through IRE‐1 endonuclease cleavage of cellular RNAs, triggers type I interferon (IFN) production in SKIV2L‐depleted cells.159 Intriguingly, THES can be caused by mutations in TTC3786, 87 where, in contrast to SKIV2L, in vitro assays do not propose a role in interferon signaling.