RanGAP1 plays a vital role in anti-infective functions of macrophages and sepsis progression.

Ran GTPase-activating protein 1 (RanGAP1) is a known regulator of nucleocytoplasmic transport; however, its specific function within innate immunity remains undefined. Here, we show that low RanGAP1 expression correlates with poor survival outcomes in septic patients and demonstrate that RanGAP1 expression and subcellular localization are dynamically regulated in macrophages following lipopolysaccharide (LPS) stimulation. We observed that deletion of RanGAP1 in macrophages exacerbates sepsis progression by using a cecal ligation and puncture (CLP) murine model. Mechanistically, RanGAP1 deficiency significantly impairs macrophage anti-infective functions, including inflammatory cytokine production, pathogen clearance, and antigen processing. These findings highlight RanGAP1 as a central regulator of macrophage immune responses, suggesting that its activity is a critical determinant of septic outcomes.