PSTPIP2 (proline-serine-threonine phosphatase interacting protein 2) is an F-BAR domain family protein that functions as a critical regulator of innate immune responses and inflammatory processes 1. The protein exhibits F-actin binding activity and participates in membrane-cytoskeleton interactions, playing key roles in macrophage activation, neutrophil migration, and cytokine production 1. PSTPIP2 acts as an anti-inflammatory mediator primarily through inhibition of IL-1β production and NF-κB pathway activation 23. Loss-of-function mutations in PSTPIP2, such as the Leu98Pro mutation in murine models, lead to autoinflammatory diseases characterized by chr18 multifocal osteomyelitis resembling human chr18 recurrent multifocal osteomyelitis 45. The protein regulates neutrophil NADPH oxidase activity, with PSTPIP2 deficiency causing elevated superoxide production and bone destruction 6. Disease manifestation involves IL-1β-mediated inflammation processed by both caspase-1 and caspase-8, and is influenced by intestinal microbiota composition 5. PSTPIP2 also regulates neutrophil extracellular trap formation through IL-19/NF-κB pathways, impacting kidney injury in aristolochic acid nephropathy 7. Low PSTPIP2 expression correlates with disease severity in sepsis patients, highlighting its clinical significance as a potential therapeutic target for autoinflammatory disorders 31.