Genetic methods (both statistical and laboratory based), along with close clinical scrutiny, have led to the recent discovery that abnormal keratin genes underlie several disorders of cornification (Table 3). The ability to classify diseases based on the specific underlying gene mutation has now become a reality (e.g., the ability to distinguish IBS from EHK and to correlate palmoplantar hyperkeratosis in EHK with keratin 1 mutations vs. the lack of palmoplantar hyperkeratosis with keratin 10 mutations). Understanding how specific keratin mutations cause their associated clinical phenotypes will lead to better appreciation of the function of KIFs in epidermis in normal and disease states.