IRHOM2: A REGULATOR OF PALMOPLANTAR BIOLOGY, INFLAMMATION AND VIRAL SUSCEPTIBILITY.

Abstract The palmoplantar epidermis is a specialised area of the skin that undergoes high levels of mechanical stress. The palmoplantar keratinisation and oesophageal cancer syndrome, Tylosis with Oesophageal Cancer, is linked to mutations in RHBDF2, encoding the proteolytically-inactive rhomboid protein, iRhom2. Subsequently, iRhom2 was found to affect palmoplantar thickening, to modulate the stress keratin response and to mediate context-dependent stress pathways via p63. iRhom2 is also a direct regulator of the sheddase, ADAM17, and the antiviral adaptor protein, STING. Here, the pleiotropic functions of iRhom2 are discussed with respect to the skin, inflammation and the antiviral response. (96 words)