In fully cornified cells, filaggrin is degraded into free amino acids. This high concentration of hydrophillic amino acids is essential for water retention and contributes to the osmolarity, and consequently the flexibility of the cornified layer (Candi et al. 2005). Filaggrin monomers are a direct target for cleavage by the aspartate-specific protease caspase 14 (Denecker et al. 2007, 2008, Hoste et al. 2011, Eckhart & Tschachler 2011). Proteases able to process profilaggrin into fillagrin in vitro include microbial ST14 (Profillagrin endopeptidase 1, PEP1), CAPN1 (mu-calpain), furin, PACE4 and matriptase MT-SP1 (Reising et al. 1995, Yamazaki et al. 1997, Pearton et al. 2001, List et al. 2003, Candi et al. 2005), but these proteases do not appear to have a role in the degradation of filaggrin that occurs at a late stage in keratinization.