Membrane-bound transcription factor site-1 protease (S1P)

Membrane-bound transcription factor site-1 protease (S1P), encoded by the MBTPS1 gene, is a serine protease belonging to the proprotein convertase subtilisin/kexin family. It is ubiquitously expressed as a type I membrane protein that localizes primarily to the Golgi apparatus. S1P plays an essential role in cleaving precursor forms of certain membrane-bound transcription factors—most notably sterol regulatory element-binding proteins (SREBPs) involved in cholesterol and fatty acid biosynthesis—and activating them through regulated intramembrane proteolysis. This process is critical for maintaining lipid homeostasis within cells. Additionally, S1P mediates endoplasmic reticulum stress responses by processing activating transcription factor 6 (ATF6), which upregulates genes encoding ER chaperones during unfolded protein response. Mutations or deficiencies in MBTPS1/S1P can result in lysosomal dysfunction and skeletal developmental disorders such as skeletal dysplasia. Experimental inhibition impairs plasma cell differentiation due to disrupted metabolic reprogramming required for high secretory activity.[1][2][3]

Other names

MBTPS1PCSK8SKI-1membrane-bound transcription factor peptidase site 1SEDKF[1][3]

Inhibition leads to reduced differentiation and function of antibody-secreting cells by blocking cleavage/activation of key transcription factors (e.g., CREB3L2, ATF6)[2].