Periphilin-1 is one of the several proteins that become sequentially incorporated into the cornified cell envelope during the terminal differentiation of keratinocyte at the outer layers of epidermis. PPHLN1 in nuclear granules and at the nuclear membrane of undifferentiated human skin keratinocytes. In differentiated keratinocytes, PPHLN1 colocalized with periplakin at the cell periphery and at cell-cell junctions.

This protein interacts with periplakin, which is known as a precursor of the cornified cell envelope. The cellular localization pattern and insolubility of this protein suggest that it may play a role in epithelial differentiation and contribute to epidermal integrity and barrier formation.