HRG1 has been identified as a cell surface and lysosomal heme transporter [2]. In addition, evidence suggests this 4TM-containing protein associates with the V-ATPase in lysosomes [1]. Recent studies confirm its lysosomal location and demonstrate that it has an important physiological function in macrophages ingesting senescent red blood cells (erythrophagocytosis), recycling heme (released from the red cell hemoglobin) from the phagolysosome into the cytosol, where the heme is subsequently catabolized to recycle the iron [3].

* Key recommended reading is highlighted with an asterisk

* Khan AA, Quigley JG. (2013) Heme and FLVCR-related transporter families SLC48 and SLC49. Mol Aspects Med, 34 (2-3): 669-82. [PMID:23506900]

1. O'Callaghan KM, Ayllon V, O'Keeffe J, Wang Y, Cox OT, Loughran G, Forgac M, O'Connor R. (2010) Heme-binding protein HRG-1 is induced by insulin-like growth factor I and associates with the vacuolar H+-ATPase to control endosomal pH and receptor trafficking. J Biol Chem, 285 (1): 381-91. [PMID:19875448]

2. Rajagopal A, Rao AU, Amigo J, Tian M, Upadhyay SK, Hall C, Uhm S, Mathew MK, Fleming MD, Paw BH et al.. (2008) Haem homeostasis is regulated by the conserved and concerted functions of HRG-1 proteins. Nature, 453 (7198): 1127-31. [PMID:18418376]

3. White C, Yuan X, Schmidt PJ, Bresciani E, Samuel TK, Campagna D, Hall C, Bishop K, Calicchio ML, Lapierre A et al.. (2013) HRG1 is essential for heme transport from the phagolysosome of macrophages during erythrophagocytosis. Cell Metab, 17 (2): 261-70. [PMID:23395172]