Prosaposin (PSAP)

Prosaposin (PSAP) is a highly conserved secreted glycoprotein that serves as the precursor of four saposin proteins (A, B, C, and D), which are essential activators for various lysosomal hydrolases involved in sphingolipid degradation[1][2][3][4]. PSAP acts as a molecular hub integrating lipid metabolism, neuronal survival, neuroprotection, immune modulation, and metabolic regulation through its cleavage products. Deficiency or mutation in PSAP leads to impaired sphingolipid catabolism, causing lysosomal storage disorders such as Gaucher disease and metachromatic leukodystrophy, as well as dysfunctional neuronal signaling and increased risk of neurodegeneration[2][3]. PSAP and its saposin derivatives are also important for immune system function, as they facilitate the presentation of lipid antigens to invariant natural killer T cells and modulate macrophage responses[2]. As a neurotrophic factor, PSAP supports synaptic plasticity and neuronal health, partially via receptor-mediated signaling through GPR37 and GPR37L1[2]. Its complex biological actions make PSAP a potential target for therapeutic intervention and a biomarker for several metabolic, neurodegenerative, and neoplastic diseases[2][3].

Other names

Saposin-ASaposin-B-ValSaposin-BSaposin-CSaposin-DGLBASAP1CSActSAP-1SAP-2Proactivator polypeptideProtein ACerebroside sulfate activatorDispersinSphingolipid activator protein 1Sulfatide/GM1 activatorA1 activatorCo-beta-glucosidaseGlucosylceramidase activatorSphingolipid activator protein 2Component CProtein Cvariant Gaucher diseasevariant metachromatic leukodystrophysaposin-Asaposin-Bsaposin-Csaposin-Dprecursor of saposinsPARK24PSAPDSAP2prosaposinproactivator polypeptidesphingolipid activator protein-1sphingolipid activator protein-2

Activation of lysosomal hydrolases (via saposin derivatives); Regulation of ganglioside and sphingolipid metabolism; Modulation of signaling pathways (ERK, PI3K/Akt, SK); Neurotrophic/receptor-mediated signaling (through GPR37 and GPR37L1); Immune cell modulation (lipid antigen presentation to iNKT cells)