Low-density lipoprotein receptor-related protein 6 (LRP6) (LRP6)

Low-density lipoprotein receptor-related protein 6 (LRP6) is a single-pass transmembrane protein that serves as an essential co-receptor in the canonical Wnt/beta-catenin signaling pathway (UniProt P49768). It functions alongside Frizzled receptors to bind Wnt ligands, which triggers a signaling cascade that inhibits the beta-catenin destruction complex, allowing beta-catenin to accumulate and translocate to the nucleus to activate gene transcription (Joiner et al., 2013). LRP6 is vital for diverse biological processes, including embryonic development, bone mineral density regulation, and glucose homeostasis. Dysregulation of LRP6 is implicated in several diseases; its overexpression is common in cancers such as breast, lung, and liver cancer, where it promotes cell proliferation and survival (Ettenberg et al., 2010). Conversely, loss-of-function mutations in LRP6 are associated with osteoporosis and early-onset coronary artery disease (Mani et al., 2007). Therapeutic approaches targeting LRP6 include monoclonal antibodies and small molecules designed to inhibit Wnt binding or receptor phosphorylation, though these must be carefully balanced to avoid toxicities in Wnt-dependent tissues like the intestinal epithelium (He et al., 2021).

Other names

LRP-6ADCAD2Low-density lipoprotein receptor-related protein 6

Inhibition of Wnt ligand binding to the extracellular domain or prevention of cytoplasmic tail phosphorylation to block beta-catenin stabilization and downstream transcription.