Defining the Critical Role of LRP4 in Neuromuscular Junctions and Bone Signaling

In this review paper, we will evaluate LRP4, a low-density lipoprotein receptor-related protein, and its many roles involving myasthenia gravis (MG), Wnt signaling, bone formation and craniofacial development. In MG, LRP4 is critical to the formation of the neuromuscular junction (NMJ) and the key function is to allow for controlled muscle contraction. LRP4 works in combination with agrin and MuSK to form the functional complex. In Wnt signaling, LRP4 was recently identified as a critical player in the pathway for both bone and tooth development and function. Its ability to act as an inhibitor sheds new light on bone formation and resorption. LRP4 binds sclerostin to LRP5 and LRP6, facilitating inhibitory effects important for bone homeostasis and remodeling. In this review paper, we will summarize the known roles of LRP4 as well as explore future directions for research surrounding LRP4 functionality.