Small proline-rich protein 2D (SPRR2D)

Small proline-rich protein 2D (SPRR2D) is a structural protein expressed in keratinocytes, initially in the cytosol and ultimately cross-linked to membrane proteins by transglutaminases to form the insoluble cornified envelope beneath the plasma membrane, which is vital for proper epidermal barrier function. SPRR2D, as part of the SPRR gene family clustered on chromosome 1q21, plays a key role in terminal keratinocyte differentiation and adaptation to environmental stress, including serving as a substrate for cornified envelope formation in the skin. In addition to conferring physical barrier function, members of the SPRR family—including SPRR2D—have recently been shown to act as epidermally produced antimicrobial proteins that protect the skin by directly disrupting bacterial membranes. Altered SPRR2D expression has been associated with conditions involving epidermal barrier dysfunction, such as psoriasis, and the gene is implicated in the pathogenesis and genetic susceptibility of these diseases. No approved drugs are currently known to target SPRR2D, and it is not considered a typical therapeutic target such as a receptor, enzyme, or transporter, but its role in skin integrity and innate immunity is significant for understanding disease mechanisms and potential future interventions.

Other names

Small proline-rich protein 2DSPRR2DSPR-2DSPR-IISmall proline-rich protein II