Low density lipoprotein receptor-related protein 4

Low density lipoprotein receptor-related protein 4 (LRP4) is a protein that in humans is encoded by the LRP4 gene. LRP4 is a member of the low-density lipoprotein (LDL) receptor family, which plays critical roles in cholesterol metabolism and signal transduction. This protein is involved in the regulation of bone formation, neuromuscular junction development, and the clearance of amyloid-beta (Aβ) peptides, an action relevant to Alzheimer's disease pathology.

Function[edit | edit source]

LRP4 acts as a receptor for agrin, a motor neuron-derived factor that is essential for the formation and maintenance of the neuromuscular junction (NMJ). The interaction between agrin and LRP4 leads to the activation of a signaling pathway that promotes the clustering of acetylcholine receptors (AChRs) at the NMJ. This process is crucial for the effective transmission of signals from nerve cells to muscle cells, facilitating muscle contraction.

In addition to its role at the neuromuscular junction, LRP4 is involved in the regulation of bone growth and remodeling. It modulates the activity of Wnt signaling, a pathway that is essential for bone development. Mutations in the LRP4 gene have been associated with bone density disorders, highlighting its importance in skeletal health.

LRP4 also plays a role in the clearance of amyloid-beta peptides, suggesting a potential link to Alzheimer's disease. By promoting the degradation of Aβ peptides, LRP4 may help prevent the formation of amyloid plaques, a hallmark of Alzheimer's pathology.

Clinical Significance[edit | edit source]

Mutations in the LRP4 gene have been linked to several human diseases. These include Sclerosteosis, a rare bone disorder characterized by excessive bone growth, and Cenani-Lenz syndactyly syndrome, a congenital condition marked by limb and kidney abnormalities. Additionally, variations in the LRP4 gene have been associated with susceptibility to common diseases such as osteoporosis and Alzheimer's disease.

Genetic and Molecular Aspects[edit | edit source]

The LRP4 gene is located on chromosome 11 in humans. It encodes a protein that is part of the LDL receptor family, known for their roles in lipid metabolism and cellular signaling. The LRP4 protein contains several domains, including LDL-receptor class A domains, EGF-like domains, and a single transmembrane domain, which are critical for its function in signaling and ligand interaction.