Low-density lipoprotein receptor-related protein 5 Low-density lipoprotein receptor-related protein 6 Kremen protein 1 (for KREMEN1) and Kremen protein 2 (for KREMEN2) (LRP5, LRP6, KREMEN1, KREMEN2)

Low-density lipoprotein receptor-related proteins 5 and 6 (LRP5, LRP6) are highly homologous, single-pass transmembrane receptors acting as essential co-receptors for Wnt ligands in the canonical Wnt/β-catenin signaling pathway. Their extracellular domains bind Wnts and inhibitors such as Dickkopf proteins (DKK1, DKK2) and sclerostin, regulating diverse biological processes like cell fate, proliferation, and tissue development. Kremen protein 1 and Kremen protein 2 are transmembrane receptors that cooperate with DKK1/2 to inhibit Wnt/β-catenin signaling by promoting endocytosis of LRP5 and LRP6, serving as key negative regulators of the pathway. The functional axis of LRP5/6–KREMEN–DKK is crucial for bone homeostasis, embryonic development, and disease, and remains a focal point for drug discovery. Mutations or altered expression of these proteins are linked to bone density disorders, cancer, and other diseases.

Other names

LDL receptor-related protein 5low-density lipoprotein receptor-related protein 5LDL receptor-related protein 6low-density lipoprotein receptor-related protein 6Kremen-1receptor for Dickkopf protein (DKK1)Kremen-2

Agonists or antagonists of Wnt signaling modulate receptor activation/inhibition. DKK1 and KREMEN1/2 act as inhibitors by promoting internalization or endocytosis of LRP5/6. Monoclonal antibodies block inhibitor binding or receptor activity.