The heme protein myeloperoxidase (MPO) is a major component of azurophilic granules of neutrophils and polymorphonuclear leukocytes. Optimal oxygen-dependent microbiocidal activity depends on MPO as the critical enzyme for the generation of hypochlorous acid and other toxic oxygen products. The MPO precursor is synthesized during the promyelocytic stage of myeloid differentiation and is subsequently processed and transported intracellularly to the lysosomes. The precursor undergoes cotranslational N-linked glycosylation to produce a glycoprotein. Glucosidases in the endoplasmic reticulum (ER) or early cis Golgi convert the pro-MPO to a form which is sorted into a prelysosomal compartment, which undergoes final proteolytic maturation to native MPO, a pair of heavy-light protomers. In normal neutrophils, MPO is expressed as a dimer. Calreticulin, a calcium-binding protein residing in the ER, interacts specifically with fully glycosylated apopro-MPO. iMPO mRNA is abundant in human promyelocytic HL-60 and mouse myeloid leukemia NFS-60 cells. MPO is expressed at high levels in circulating neutrophils and monocytes but is not detectable in microglia, brain-specific macrophages or normal brain tissue.