Hemopexin (HPX) is a plasma protein that binds heme and transports it to the liver for breakdown and iron recovery, after which free hemopexin returns to circulation [UniProt]. Beyond its classical heme-scavenging role, HPX has emerged as a multifunctional regulator with broader physiological significance. Mechanistically, HPX operates through multiple pathways. In intestinal and hepatic contexts, HPX suppresses cell proliferation and migration while inhibiting MAPK signaling activation 1. HPX also protects against lipopolysaccharide-induced epithelial damage by reducing apoptosis and maintaining tight junction integrity through ZO-1 expression 2. In hemolytic conditions, HPX therapy reduces free heme-mediated oxidative stress, thereby decreasing atherosclerotic plaque accumulation 3. Clinically, HPX demonstrates prognostic significance across multiple diseases. High HPX levels predict poor prognosis in older colorectal cancer patients 4, while low HPX associates with gastric lesion progression risk and early gastric cancer development 5. In hepatocellular carcinoma, HPX downregulation contributes to lenvatinib resistance through MAPK pathway activation, suggesting HPX restoration as a therapeutic strategy 1. Additionally, genetic variants at the HPX locus associate with nine plasma proteins, indicating pleiotropic effects on cardiovascular homeostasis 6. These findings position HPX as both a biomarker and potential therapeutic target across hemolytic, gastrointestinal, and malignant diseases.