PLS is caused by homozygous (2/3 of the cases) or compound heterozygous (1/3 of the cases) pathogenic variants in the gene CTSC that encodes a lysosomal cysteine protease called cathepsin C (CTSC) or dipeptidyl peptidase I (103, 104). This evidence concerns the gene CTSB and Papillon-Lefèvre syndrome.