RHBDF2 and Non-epidermolytic palmoplantar keratoderma: Studies of Rhbdf1 and Rhbdf2 GOF mutant mice (Fig. 2D, E)—Rhbdf1viable (Hosur et al. 2020), curly bare (Rhbdf2cub), uncovered (Rhbdf2uncv), and CRISPR/Cas9-mediated genetically engineered mouse model of tylosis with esophageal cancer (Rhbdf2TOC)—suggest that RHBDF1 and RHBDF2 have distinct functions, and thereby distinct physiological targets.