Tylosis with esophageal cancer (TOC) is an autosomal-dominant syndrome characterized by palmoplantar keratoderma, oral precursor lesions, and a high lifetime risk of esophageal cancer. It has been reported that mutations in RHBDF2 cause this disease. RHBDF2 is an inactive rhomboid protease, which has recently been shown to regulate the maturation of the multi-substrate ectodomain sheddase enzyme ADAM17 in macrophages.
