Profilaggrin, an insoluble precursor of the intermediate filament-associated protein filaggrin,
contains multiple internal repeats (PIRs). At terminal differentiation of epidermis, proteolytic
processing within a" linker" region of each PIR releases soluble filaggrin in a two-stage
process. The first stage endoproteinase (PEP1, profilaggrin endoproteinase 1) cleaves
mouse profilaggrin at a subset of the linkers, yielding processing intermediates consisting of
several filaggrin repeats. An epidermal endoproteinase that cleaves the requisite linker …