Figure 6. Summary of proposed function for SePP in Se transport and storage.

The current model states that dietary Se compounds are taken up by the liver, where selenoproteins, including SePP, are synthesized. SePP is secreted into plasma and provides Se to the rest of the body. The kidney takes up liver-derived SePP from plasma for biosynthesis of selenoproteins, including eGPx. A similar scenario was expected for brain. However, in the absence of hepatic selenoprotein biosynthesis, plasma SePP and plasma Se levels are severely reduced, but brain selenoprotein metabolism remains unaffected, indicating an alternative route for Se uptake available to the brain. We propose SePP to also serve as a local Se storage and recycling protein. All available Se not needed to maintain selenoenzyme activities is incorporated into SePP to serve as an extracellular Se store. After proteolytic cleavage, the Se-rich C-terminus is taken up by the neuron and re-used for selenoprotein biosynthesis. Thus genetic inactivation of SePP compromises brain selenoprotein metabolism and Se retention, while liver-specific inactivation of SePP does not affect brain Se status, selenoprotein biosynthesis or Se retention.