PTX3 (pentraxin 3) is a secretory pattern recognition receptor that serves as a multifaceted regulator of innate immunity and tissue homeostasis. Primarily, PTX3 functions in inflammatory regulation and pathogen resistance through complement activation and immune cell modulation 1. Mechanistically, PTX3 regulates macrophage polarization and infiltration in tissue microenvironments. In glioblastoma, PTX3 mediates macrophage infiltration, migration, and inflammation-resolving-polarization, thereby modulating an immunosuppressive microenvironment 2. Conversely, in hepatic ischemia-reperfusion injury, PTX3 promotes M1 macrophage polarization, exacerbating hepatocyte pyroptosis 3. PTX3 expression is epigenetically regulated through the PRMT1-histone methylation axis and post-transcriptionally controlled via m6A-YTHDF3-dependent mRNA degradation 45. Beyond macrophage regulation, PTX3 is strategically localized in lymphatic vessel extracellular matrix, where it organizes lymphatic architecture and enables dendritic cell trafficking 6. Clinically, PTX3 emerges as a significant biomarker: elevated plasma levels associate with leprosy susceptibility and decrease after treatment 1, while high PTX3 expression in gliomas correlates with poor prognosis, higher WHO grade, and altered immune infiltration patterns 7. Additionally, PTX3 contributes to endothelial dysfunction by suppressing nitric oxide synthesis and promoting vascular inflammation 8, suggesting therapeutic potential in multiple disease contexts.