Low density lipoprotein receptor adaptor protein 1 (LDLRAP1)

Low density lipoprotein receptor adaptor protein 1 (LDLRAP1) is a cytosolic adaptor protein, crucial for the internalization of low-density lipoprotein receptors (LDLR) in clathrin-mediated endocytosis, particularly in the liver[1][2][3][4][5]. It contains a phosphotyrosine binding domain (PTB), which specifically interacts with the NPXY motif in the cytoplasmic tail of LDLR[1][2][4][5]. Mutations in LDLRAP1 impair LDLR trafficking and result in autosomal recessive hypercholesterolemia—a genetic disorder characterized by elevated cholesterol levels and increased cardiovascular risk[1][2][3][5]. Beyond its core function in LDLR endocytosis and cholesterol clearance, LDLRAP1 also contributes to basolateral sorting of membrane proteins in polarized cells and can be regulated by microRNAs[1]. Loss-of-function mutations or regulatory disruptions in LDLRAP1 can severely compromise cholesterol homeostasis, leading to pathogenic lipid accumulation and amplified risk of heart disease[1][2][5].

Other names

ARHARH1ARH2FHCB1FHCB2MGC34705DKFZp586D0624Autosomal recessive hypercholesterolemia proteinLDL receptor adaptor protein