PLS is a rare autosomal recessive disease in which DPP1 insufficiency, which is caused by a mutation in the DPP1 gene (CTSC), results in diffuse palmoplantar hyperkeratosis, severe prepubertal periodontitis, and premature loss of both deciduous and permanent teeth (26, 46). Here, CTSC is linked to diffuse palmoplantar keratoderma.