Netherton syndrome (NS, OMIM 256500) is a rare autosomal recessive disorder 
manifesting with congenital ichthyosis, a specific hair shaft abnormality named 
trichorrhexis invaginata, and atopic manifestations. Because of severe 
complications frequently occurring in the neonatal period, NS prognosis can be 
poor in infancy. NS is due to loss-of-function mutations in the SPINK5 gene and 
to the consequent lack of expression of its encoded protein LEKTI in the skin 
and all stratified epithelial tissues. Following the identification of the NS 
causative gene and protein, specific diagnostic tools have been developed, thus 
breaking up the challenge of distinguishing NS from other congenital ichthyoses 
with overlapping features, and from severe, early-onset forms of atopic 
dermatitis or psoriasis. Intensive efforts to extend the knowledge into the 
pathomechanisms of NS have also been made. However, NS management is still 
problematic due to the lack of specific treatment and unmet needs. This overview 
summarizes the current state of the art in NS research with an emphasis on the 
progress made toward disease-specific innovative therapy development.