NIPAL4 and Hyperkeratosis: Interestingly, histological analyses in the epidermis of Nipal4-knockout mice model showed several morphological abnormalities including hyperkeratosis, impairment of lipid multilayer structure formation, immature keratohyalin granules as well as decreasing level of the skin barrier lipid acylceramide that further support the histological observations in the proband [52].