Site-1 Protease (S1P)

Site-1 protease (S1P), also known as SKI-1 or PCSK8, is a serine protease that plays a central role in regulated intramembrane proteolysis. It is crucial for activating sterol regulatory element-binding proteins (SREBPs), which regulate cholesterol and fatty acid synthesis. S1P also activates ATF6 during ER stress and is involved in lysosome biogenesis. It is a potential drug target for lipid-lowering therapies, but its inhibition requires careful consideration due to its diverse roles and potential developmental consequences.

Other names

Membrane-bound transcription factor peptidase, site 1Subtilisin/kexin-isozyme 1SKI-1PCSK8SEDKF

S1P cleaves specific substrates at non-basic residues after hydrophobic or small amino acids if Arg or Lys is at position P4. This cleavage activates key transcription factors such as SREBPs and ATF6, influencing lipid metabolism, ER stress response, and lysosome biogenesis.