ST14 (Suppressor of tumorigenicity 14, also known as matriptase) associated with the plasma membrane catalyzes the hydrolytic cleavage of proKLK5 (pro-Kallekrein-5) to yield active KLK5 enzyme. The activity of human ST14 enzyme is inferred from that of its well-characterized mouse homolog (Sales et al. 2010). Consistent with this inference, deficiencies of the human enzyme are associated with an ichthyosis syndrome (MIM 602400) as is a knockout mutation of mouse St14 (Alef et al. 2009).

Filaggrin is initially synthesized as a large, insoluble, highly phosphorylated precursor containing many tandem copies of 324 residues. This precursor is dephosphorylated and proteolytically cleaved by several proteases, including the undefined protease PEP1 (Resing et al. 1996), mu-calpain (Yamazaki et al. 1997), furin, PCSK6 (PACE4) (Pearton et al. 2001), PRSS8 (cap1) (Leyvraz et al. 2005), ST14 (matriptase) (List et al. 2003), CELA2 (Bonnart et al. 2010), CASP14 (Denecker et al. 2007) and Kallikrein-related peptidase 5 (KLK5) (Sakabe et al. 2013). Filaggrin is further processed and proteolytically degraded by CASP14 (Eckhart & Tschachler 2011).

Filaggrin is initially synthesized as a large, insoluble, highly phosphorylated precursor containing many tandem copies of 324 residues. This precursor is dephosphorylated and proteolytically cleaved by several proteases, including the undefined protease PEP1 (Resing et al. 1996), mu-calpain (Yamazaki et al. 1997), furin, PCSK6 (PACE4) (Pearton et al. 2001), PRSS8 (cap1) (Leyvraz et al. 2005), ST14 (matriptase) (List et al. 2003), CELA2 (Bonnart et al. 2010), CASP14 (Denecker et al. 2007) and Kallikrein-related peptidase 5 (KLK5) (Sakabe et al. 2013). Filaggrin is further processed and proteolytically degraded by CASP14 (Eckhart & Tschachler 2011).

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.