Syndecan-1 shedding by meprin β impairs keratinocyte adhesion and differentiation in hyperkeratosis

•Fra-2 transgenic mice exhibit increased meprin β expression and proteolytic activity in the skin.•Expression of meprin β under the Krt5-promotor in mice leads to hyperkeratosis, marbled pigmentation and skin inflammation.•N-terminomics and cell based assays identified how pathological induction of meprin β leads to hyperkeratosis.•Cleavage of syndecan-1 by meprin β leads to impaired adhesion and differentiation of primary keratinocytes.