Low density lipoprotein receptor-related protein-associated protein 1 (LRPAP1)

Low density lipoprotein receptor-related protein-associated protein 1 (LRPAP1), also known as receptor-associated protein (RAP), is a molecular chaperone that binds the LDL receptor family (including LRP1, LRP2, ApoER2, VLDLR, and LDLR) in the endoplasmic reticulum, aiding their proper folding and trafficking to the cell surface. LRPAP1 acts as a potent inhibitor and antagonist of ligand binding to these receptors, with nanomolar affinity, blocking interactions with a wide range of physiological ligands (e.g., apolipoprotein E, α2-macroglobulin, amyloid beta). Physiologically, LRPAP1 influences cellular processes such as endocytosis, phagocytosis, chemotaxis, and cell signaling. In activated microglia, extracellular LRPAP1 can inhibit phagocytosis and amyloid beta aggregation, potentially affecting neurodegenerative disease progression. LRPAP1 also mediates immune regulation by binding the type I interferon receptor IFNAR1, promoting its degradation and thereby enabling viruses to evade host antiviral defenses. Mutation in LRPAP1 gene is linked to forms of familial high myopia. There are no clinically approved drugs targeting LRPAP1, but potential therapeutic strategies may involve modulating its chaperone or antagonist activities. Safety considerations include the risk of immune or neurodevelopmental dysfunction if LRPAP1 pathways are altered.

Other names

Alpha-2-macroglobulin receptor-associated proteinA2MRAPReceptor-associated protein (RAP)HBP44MRAPA2RAPMYP2339 kDa receptor-associated proteinLow density lipoprotein receptor-related protein-associated protein 1Low density lipoprotein-related protein-associated protein 1

Chaperones LDL receptor family proteins, preventing premature ligand binding during protein trafficking and maturation. Acts as a competitive antagonist at the ligand-binding sites of LDL receptor family proteins, inhibiting binding of natural ligands including ApoE and amyloid beta. Promotes degradation of interferon receptor IFNAR1 during viral infection, thereby suppressing antiviral immune signaling pathways.