Together, these results, along with the recent findings that mutations in Rhbdf2 in mice result in enhanced EGFR pathway activation (Hosur et al., 2014; Siggs et al., 2014), suggest a possible mechanism for the association between RHBDF2 mutations and tylosis. The gene discussed is RHBDF2; the disease is Non-epidermolytic palmoplantar keratoderma.