PF4 (platelet factor 4/CXCL4) is a cationic chemokine primarily released from platelet α-granules that plays critical roles in hematopoiesis, thrombosis, and inflammation. PF4 maintains hematopoietic stem cell (HSC) quiescence and prevents HSC aging by binding to receptors including LDL receptor and CXCR3, with PF4 deficiency accelerating HSC aging phenotypes 1. The protein forms tetramers with high positive charge that bind polyanions like heparin, creating complexes that can trigger pathogenic antibody responses in heparin-induced thrombocytopenia (HIT) and vaccine-induced immune thrombocytosis and thrombosis (VITT) 23. PF4 drives tissue fibrosis by promoting profibrotic macrophage differentiation and myofibroblast formation through internalization via surface glycosaminoglycans 45. In atherosclerosis, PF4 induces a distinct M4 macrophage phenotype characterized by CD68+/S100A8+/MMP7+ expression and loss of CD163, contributing to plaque instability 6. Additionally, PF4 exhibits antimicrobial properties by enhancing pathogen clearance and modulating neutrophil extracellular trap formation 7. The protein's pleiotropic effects make it both protective in hematopoiesis and antimicrobial responses, yet pathogenic in thrombotic and fibrotic disorders 8.