Inflammatory bowel diseases (IBDs), such as Crohn's disease and ulcerative colitis, are a group of disorders characterised by breakdown of the intestinal epithelium. These disorders have been linked to multiple genetic loci, which has made identification of causative mutations particularly difficult. Mutations in keratin intermediate filaments can severely disrupt tissue integrity in the skin, producing skin-blistering conditions such as epidermolysis bullosa simplex (EBS). Since keratins are also present in the gut epithelium, Birgit Lane and co-workers speculated that keratin mutations might also play a part in IBD. Indeed, they have now identified several missense keratin 8 (K8) mutations in patients who have Crohn's disease or ulcerative colitis (see p. 1989). These mutations lie outside the `hotspots' associated with the skin-blistering syndromes. However, the authors find that they disrupt assembly of keratin filaments both in vitro and in vivo. Moreover, in response to oxidative stress, one (K8 G62C) generates keratin...

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