EVPL

EVPL Full Name

envoplakin

EVPL Introduction

Envoplakin (EVPL) is a precursor component of the cornified envelope of stratified epithelia and the first member of the plakin family shown to be targeted to keratinocyte cell envelopes. The human gene maps to chromosome 17q25.1, adjacent to its close relative periplakin, and encodes a ~200 kDa rod-shaped protein with an N-terminal plakin domain, a central coiled-coil rod, and a C-terminal pair of tandem globules that mediate interactions with the keratin intermediate filament network. EVPL expression is induced during terminal differentiation of keratinocytes, where it becomes cross-linked by transglutaminases into the insoluble cornified layer.

Figure 1. The structure of EVPL.

Assembly of the Cornified Cell Envelope
During the late stages of epidermal differentiation, envoplakin is recruited to the plasma membrane via its N-terminal domain, where it oligomerizes with periplakin and is then cross-linked to itself, to periplakin, and to small proline-rich proteins through isopeptide bonds catalyzed by transglutaminase 1 and 3. This generates a 15-nm-thick protein scaffold on the cytoplasmic face of the corneocyte that anchors keratin bundles and prevents their collapse under mechanical stress. EVPL also contributes to the formation of desmosomes and the keratinocyte cell periphery, working alongside desmoplakin to tether intermediate filaments to cell–cell junctions. Its absence in EVPL-null mice produces fragile cornified envelopes and increased transepidermal water loss.

Skin Barrier Defects and Autoimmune Disease
Although complete loss of envoplakin is not lethal, EVPL deficiency sensitizes mice to epidermal barrier disruption and delays wound re-epithelialization. In humans, single-nucleotide polymorphisms in the EVPL locus have been associated with atopic dermatitis and with susceptibility to contact dermatitis, consistent with its role in barrier integrity. Autoantibodies directed against envoplakin and periplakin are a hallmark of paraneoplastic pemphigus, a mucocutaneous disease in which tumor-driven immune cross-reactivity against plakin antigens triggers severe stomatitis and polymorphic skin lesions.

Alternate Names for EVPL

EVPL; envoplakin; EVPK; 210 kDa cornified envelope; 210 kDa paraneoplastic pemphigus antigen; p210; 210 kDa cornified envelope precursor protein