LRP4 (LDL receptor-related protein 4) is a critical cell surface receptor mediating neuromuscular junction (NMJ) formation and maintenance. At the NMJ, LRP4 directly binds AGRIN and recruits it to the MUSK signaling complex, facilitating AGRIN-induced MUSK phosphorylation and subsequent acetylcholine receptor clustering at the postsynaptic membrane 1. LRP4 also functions in negative regulation of canonical Wnt signaling through interaction with SOST and antagonism of LRP6-mediated pathway activation. LRP4 is clinically significant as an autoimmune target in myasthenia gravis (MG), a neuromuscular junction disorder characterized by muscle weakness and fatigue 2. Serum antibodies against LRP4 are identified in less than 1% of MG patients 3, forming a distinct serologic MG subclass 4. LRP4-antibody MG represents an emerging entity potentially including agrin-associated cases 2. Like other MG forms, LRP4-MG requires immunosuppressive treatment, with emerging therapies such as nipocalimab (a neonatal Fc receptor blocker) showing efficacy in antibody-positive MG patients 5. Genetic mutations in LRP4 cause congenital myasthenic syndrome type 17 and skeletal disorders including Cenani-Lenz syndactyly syndrome and sclerosteosis 2, highlighting LRP4's essential roles in NMJ development and bone metabolism.