LRP4 is a cell surface receptor essential for neuromuscular junction (NMJ) formation and maintenance. It directly binds agrin and recruits it to the MUSK signaling complex, mediating agrin-induced MUSK phosphorylation and subsequent acetylcholine receptor clustering at the postsynaptic membrane. LRP4 also functions as a co-receptor for sclerostin (SOST), facilitating its inhibition of Wnt signaling and bone formation. Pathogenic variants in LRP4 cause congenital myasthenic syndrome 17, a rare genetic disorder of neuromuscular transmission characterized by impaired muscle contraction. LRP4-specific autoantibodies account for less than 1% of myasthenia gravis cases but represent a distinct serologic subgroup with particular clinical features 1. Patients with LRP4 autoimmune myasthenia gravis are classified separately from those with acetylcholine receptor or muscle-specific kinase antibodies due to differences in treatment responsiveness and disease mechanisms 2. Recent clinical trials demonstrate that neonatal Fc receptor blockade with nipocalimab provides clinically meaningful improvements in patients with antibody-positive generalized myasthenia gravis, including those with anti-LRP4 antibodies 3. While standard immunosuppressive treatments form the mainstay of therapy, emerging mechanistic approaches targeting B cells, complement, and antibody clearance pathways offer new options for LRP4-associated disease.