HPR (haptoglobin-related protein) is a primate-specific plasma protein that functions primarily in innate immune defense against African trypanosomes and hemoglobin homeostasis 1. As a gene duplication product of haptoglobin, HPR shares structural similarity enabling hemoglobin binding with high affinity 1. HPR's critical immune function involves association with apolipoprotein L-I (apoL-I) in high-density lipoprotein particles termed trypanosome lytic factor-1 (TLF-1) 2. These HDL particles are internalized by African trypanosomes through the parasites' hemoglobin-haptoglobin receptor, which cannot discriminate between haptoglobin and HPR 2. Once internalized, apoL1 forms anionic pores in lysosomal membranes, triggering osmotic lysis and parasite death, thereby conferring human protection against many trypanosome species 2. Additionally, HPR may contribute to hemoglobin detoxification and clearance of cell-free hemoglobin to facilitate hepatic heme-iron recycling, similar to haptoglobin 1. HPR is transcriptionally active in human tumor cell lines including hepatoma and leukemia cells 3. Understanding HPR's structural properties may facilitate development of therapeutic derivatives for hemolytic diseases and hemoglobinopathies 1. HPR genetic polymorphisms show population-specific distributions associated with serum haptoglobin and cholesterol levels 4.