LRP4

LRP4 (low-density lipoprotein receptor-related protein 4) is a member of the LDL receptor-related protein family. The human LRP4 gene encodes a single-pass transmembrane receptor expressed in skeletal muscle and various tissues, with an extracellular ligand-binding region and a cytoplasmic tail that participates in intracellular signaling.

LRP4 is best known for its role at the neuromuscular junction, where it binds agrin and promotes MuSK activation, leading to clustering of acetylcholine receptors at the postsynaptic membrane, a key step in NMJ formation and maintenance.

Beyond NMJ signaling, LRP4 participates in broader signaling networks by modulating signaling pathways such as BMP and Wnt in a tissue-specific manner.

Clinical significance: Autoantibodies to LRP4 have been detected in a subset of patients with myasthenia gravis, indicating a role at the peripheral synapse in humans. Rare pathogenic variants in LRP4 have been associated with congenital skeletal malformations and limb anomalies in some families or case reports, underscoring its importance in development.

Research: LRP4 is studied as a focal point of NMJ biology and as a modulator of signaling in bone and other tissues, with potential implications for neuromuscular disorders and skeletal diseases.