ORF is 981 bp in length and encodes for a 327-amino acid protein. TRAP is translated as a single polypeptide. TRAP gene transcription is regulated by the Microphthalmia-associated transcription factor. Physiology and pathology Many functions have been attributed to TRAP, and its physiologic role(s) are likely to be manifold. The mice knockout studies as well as the human disorder associated with genetic deficiency of TRAP shed some light onto its functions. In knockout studies, TRAP−/− mice exhibit mild osteopetrosis, associated with reduced osteoclast activity. These result in thickening and shortening of the cortices, formation of club-like deformities in the distal femur, and widened epiphyseal growth plates with delayed mineralization of cartilage, all of which increase with age. In TRAP overexpressing transgenic mice, mild osteoporosis occurs along with increased osteoblast activity and bone synthesis. Proposed functions of TRAP include osteopontin /bone sialoprotein dephosphorylation, the generation of reactive oxygen species (ROS), iron transport, and as a cell growth and differentiation factor. Genetic deficiency of TRAP, determined by biallelic recessive mutations in the ACP5 gene, are the basis of the human disorder spondylenchondrodysplasia. The clinical phenotype involves the bone, the central nervous system, and the immune system. The pathogenesis probably includes a defect in bone reabsorption as well as immune dysregulation because of impaired dephosphorylation of osteopontin, but may be more complex and needs to be elucidated further. Protein dephosphorylation and osteoclast migration It has been shown that osteopontin and bone sialoprotein, bone matrix phosphoproteins, are highly efficient in vitro TRAP substrates, which bind to osteoclasts when phosphorylated. Upon partial dephosphorylation, both osteopontin and bone sialoprotein are incapable of binding to osteoclasts. From this effect, it has been hypothesized that TRAP is secreted from the ruffled border, dephosphorylates osteopontin and allows osteoclast migration, and further resorption to occur. ROS generation Reactive oxygen species (ROS) are generated in macrophages and osteoclasts from superoxide (O2−.), which forms from the action of NADPH-oxidase on oxygen (O2). They play an essential role in the function of phagocytic cells. TRAP, containing a redox active iron, catalyzes the generation of ROS through Fenton chemistry: O2 → (NADPH-oxidase) O2− ∙ → (superoxide dismutase) H2O2 → (catalase) H2O + O2 TRAP-Fe3+ (purple) + O2− ∙→ TRAP-Fe2+ (pink) + O2 H2O2 + TRAP-Fe2+ (pink) → HO∙ + HO− + TRAP-Fe3+ producing hydroxyl radicals, hydrogen peroxide, and singlet oxygen. In osteoclasts, ROS are generated at the ruffled border and seem to be required