The present invention relates to a polynucleotide encoding the corneodesmosin protein having one or more nucleotide insertions, deletions or substitutions at one or novel positions. The invention also relates to the corneodesmosin protein having one or more amino acid insertions, deletions and substitutions. These nucleotide and amino acid polymorphisms are useful in diagnosing or determining susceptibility to corneodesmosin-mediated disease, for example inflammatory diseases including psoriasis, and in treating such disease. Host cells and transgenic non-human animals comprising polynucleotides or proteins of the invention are provided. Methods of screening for agents for use in treating corneodesmosin-mediated disease are also provided.