Dominant active iRhom2 mutations, within the N-terminal cytoplasmic tail, cause a rare condition known as tylosis with esophageal cancer, characterized by hyperproliferation of epidermal cells, leading to thickening of the skin on palms and soles, and increased susceptibility to cancer of the esophagus [98,99]. The gene discussed is RHBDF2; the disease is esophageal cancer.