Signal peptide peptidase-like 2A (SPPL2A)

Signal peptide peptidase-like 2A (SPPL2A) is a lysosomal, intramembrane-cleaving aspartic protease of the GXGD family, localized to late endosomal and lysosomal membranes[1][2][3]. It is essential for immune cell function by cleaving the invariant chain CD74, which is key for the maturation of MHC class II complexes and antigen presentation in B cells and dendritic cells[1][2][3][4]. SPPL2A also cleaves the transmembrane fragments of substrates such as tumor necrosis factor alpha (TNFα), Fas ligand (FASLG), ITM2B, and viral glycoproteins[1][2][3][4]. Deficiency or inhibition of SPPL2A disrupts B cell maturation and immune responses, and mutations are associated with immunodeficiency syndromes[4]. As a critical regulator of antigen presentation, SPPL2A is considered a potential therapeutic target in immune-related diseases, though inhibition carries potential risks of causing immunodeficiency[4].

Other names

IMP3PSL2PSEC0147SPP-like 2ASPPL2aIMP-3Intramembrane protease 3Presenilin-like protein 2IMD86

Inhibition of SPPL2A prevents cleavage of the invariant chain CD74, leading to modulation of antigen presentation and B cell maturation[4]