Selenoprotein P (SELENOP) (SELENOP)

Selenoprotein P (SELENOP) is a secreted glycoprotein primarily produced by the liver that functions as the major selenium transporter in human plasma [1, 3]. It is unique among selenoproteins for containing multiple selenocysteine (Sec) residues—typically ten in humans—organized into two distinct functional domains: an N-terminal catalytic domain and a C-terminal transport domain [4]. The N-terminal domain contains a UxxC redox motif that provides glutathione peroxidase-like antioxidant activity, protecting against lipid peroxidation [3]. The C-terminal domain contains the majority of the Sec residues and is dedicated to delivering selenium to high-priority tissues like the brain and kidneys via receptor-mediated endocytosis [1, 4]. Beyond its physiological role in selenium homeostasis, SELENOP has been identified as a hepatokine that induces insulin resistance in skeletal muscle and the liver, making it a significant therapeutic target for type 2 diabetes and metabolic syndrome [2]. Therapeutic strategies currently under investigation include the use of neutralizing antibodies or small molecules to reduce SELENOP levels or activity to restore glucose tolerance [2, 4].

Other names

SEPP1SEPPSelenoprotein P1Plasma selenoprotein P

Selenium transport and delivery to peripheral tissues via LRP8 and LRP2 receptors; reduction of phospholipid hydroperoxides via N-terminal catalytic domain; modulation of insulin signaling pathways.