SPINK5 and Netherton syndrome: Although FLG mutations are the most significant mutations associated with AD, many other genes involved in skin barrier function have been implicated, including SNPs in the SPINK5 gene.30, 31 Homozygous or compound heterozygous loss-of-function mutations in the SPINK5 gene result in the autosomal recessive disorder Netherton syndrome, with severe AD and allergy.1