SERPINB9

SERPINB9, also known as serpin peptidase inhibitor clade B member 9, is a protein-coding gene in humans that encodes an inhibitor of serine proteases. The protein is a member of the serpin superfamily and functions primarily as a cytotoxic granzyme B inhibitor. Structurally, SERPINB9 adopts the canonical serpin fold, featuring a reactive center loop that traps target proteases in a covalent complex.

The SERPINB9 gene is located on chromosome 18q21.31 and is expressed in many lymphoid tissues, with high levels in cytotoxic T lymphocytes and natural killer cells. Its expression is inducible by interferon gamma and other cytokines involved in immune activation. By binding granzyme B released during the immunological synapse, SERPINB9 protects target cells from perforin‑dependent apoptosis, thereby regulating the cytotoxic activity of immune cells.

Altered SERPINB9 expression has been implicated in several disease contexts. Overexpression has been reported in various cancers, including melanoma and hepatocellular carcinoma, and is thought to contribute to immune evasion by blocking granzyme B‑mediated tumor cell death. Conversely, reduced SERPINB9 levels in certain autoimmune conditions may enhance susceptibility to cytotoxic damage. Additionally, mutations in SERPINB9 have been linked to rare cases of hereditary ichthyosis with immunologic abnormalities.

SERPINB9 interacts with multiple proteins involved in immune regulation. It forms complexes with pagI, a protease that modulates its activity, and interacts indirectly with the protein kinase C pathway through downstream signaling partners. Despite its modest size, SERPINB9 plays a pivotal role in fine‑tuning immune responses by controlling granzyme B activity.