Moreover, skin barrier dysfunctions are one of the major factors involved in AD development.[2] The gene SPINK5 is located on chromosome 5q31-32, which encodes the skin barrier protein lympho-epithelial Kazal-type-related inhibitor (also known as serine protease inhibitor Kazal-type 5).[21,22]SPINK5 in the epidermis is primarily expressed in the stratum granulosum, where it functions as a protease. This evidence concerns the gene SPINK5 and Alzheimer disease.