Proline-serine-threonine phosphatase-interacting protein 2 (PSTPIP2)

Proline-serine-threonine phosphatase-interacting protein 2 (PSTPIP2) is an adaptor protein predominantly expressed in macrophages and their precursors, notable for its F-BAR domain that binds to and bundles F-actin, thereby regulating actin cytoskeleton dynamics, membrane curvature, cell migration, and immune cell functions[1][2][4][5]. It acts as a negative regulator of inflammation by inhibiting cytokine production (such as IL-1β, CXCL2, and reactive oxygen species from NOX2 NADPH oxidase in neutrophils) and by suppressing osteoclastogenesis, maintaining bone and immune homeostasis[2][4]. Pathogenic mutations in PSTPIP2 disrupt immune regulation and are causative for autoinflammatory syndromes like chronic recurrent multifocal osteomyelitis (CRMO) and other inflammatory bone conditions[1][2][3][5]. PSTPIP2 interacts with immune regulatory phosphatases including PTP-PEST, SHIP1, and CSK, and exerts its immunosuppressive functions by integrating signals at the cytoskeleton-membrane interface[2][4]. As a disease-linked immunomodulatory protein, it is emerging as a potential biomarker and therapeutic target for autoinflammatory, inflammatory bone, and potentially other immune-mediated diseases, although no current drug interactions or clinical inhibitors are established[2][5].

Other names

PEST phosphatase-interacting protein 2MAYPMacrophage F-actin-associated and tyrosine phosphorylated proteinPPIP2