Signal peptide peptidase (SPP)

Signal peptide peptidase (SPP), encoded by the HM13 gene, is an intramembrane aspartic protease localized to the endoplasmic reticulum. It catalyzes the intramembrane cleavage of signal peptides that have been removed from precursors of secretory and membrane proteins, thereby releasing peptide fragments into the cytosol. SPP is essential for generating immune epitopes (HLA-E), facilitates processing of viral proteins including hepatitis C virus core protein, and plays a role in regulating autophagy and ER-stress pathways. Aberrant SPP/HM13 expression has been implicated in cancer progression, especially breast cancer, where high expression correlates with enhanced proliferation, metastasis, PI3K-AKT-mTOR pathway activation, and poor prognosis. SPP is part of the presenilin-type aspartic protease family and is a potential therapeutic target under investigation for oncology and other disease contexts[1][2][3][4][6].

Other names

Minor histocompatibility antigen H13HM13H13IMP1IMPASIMPAS-1MSTP086PSENL3PSL3SPPL1dJ324O17.1Presenilin-like protein 3Signal peptide peptidase-like 1Intramembrane protease 1Signal peptide peptidase beta

Inhibitors block intramembrane proteolysis and downstream signaling, potentially impacting autophagy and ER-stress pathways in cancer. Modulation of SPP affects PI3K-AKT-mTOR signaling and autophagic flux in tumor models.