RHBDF2 and Non-epidermolytic palmoplantar keratoderma: Additional evidence for a regulatory role of the iRhom2 N terminus comes from the identification of gain of function mutations in the N terminus of human iRhom2 that enhance TACE sheddase activity (Maney et al., 2015) and cause tylosis with esophageal cancer, a keratinocyte hyperproliferative condition (Blaydon et al., 2012).