The SERPINB8 gene encodes a protein belonging to the high molecular weight serine proteinase inhibitor (SERPIN) superfamily. Members of this family contain a highly-conserved surface-exposed reactive site loop (RSL), which interacts with the target protease to form tight, irreversible complexes. In addition to the RSL, the SERPINB8 protein contains two hydrophobic regions in close proximity to the N terminus, believed to be important for secretion and allowing SERPINB8 to reside either intracellularly or extracellularly.
SERPINs are responsible for a diverse set of intracellular and extracellular functions including cellular differentiation, tumor suppression, apoptosis, and cell migration. While the specific function of SERPINB8 has not been fully characterized, recent knockdown studies in human keratinocytes have shown that in the absence of SERPINB8, there is a cell-cell adhesion defect, which is heightened by mechanical stress. The gene has thus been implicated in Peeling Skin Syndrome 5 (PSS5), a genodermatosis characterized by superficial peeling of the dorsal and palmar skin of the hands and feet.