Selenoprotein S (SELENOS)

Selenoprotein S (SELENOS) is a small, intrinsically disordered membrane protein localized primarily in the endoplasmic reticulum, where it functions as both a recruiter/adaptor and a potential enzyme due to its rare selenocysteine-containing loop. It plays a central role in ER-associated degradation (ERAD) by facilitating the removal of misfolded proteins, partners with p97/VCP ATPase, and anchors protein complexes to the ER membrane. SELENOS also regulates inflammation by moderating cytokine secretion (including IL-6, IL-1β, TNF-α), responds dynamically to cellular stress, and participates in signaling pathways. Its genetic and expression variance is linked to multiple diseases, including diabetes, cardiovascular disease, several cancers, and sepsis. Additionally, SELENOS is hijacked by viral infections such as SARS-CoV-2 for replication complex formation. The exact mechanisms underlying its functions are under active investigation due to the protein's inherently disordered structure and broad interactome.

Other names

SELENOSSelSSEPS1VIMPTANISAD-015SBBI8MGC2553VCP-interacting membrane proteinValosin-containing protein-interacting membrane protein

Hypothetical mechanisms (as no direct drugs are approved): Modulation of SELENOS expression or activity to regulate ER stress, reduce cytokine-mediated inflammation, or alter redox signaling. Targeting its protein-protein interactions (such as with p97/VCP complex) for control of proteostasis in disease states.