AGRN (agrin) is an extracellular matrix protein critical for neuromuscular junction (NMJ) development and function. It serves as a heparan sulfate proteoglycan that mediates receptor clustering and transmembrane receptor protein tyrosine kinase activation, essential processes for establishing stable neuromuscular synapses 1. AGRN functions through multiple mechanisms: it promotes filopodia assembly and dendritic filopodia induction in a splice-variant-dependent manner, binds dystroglycan and other basement membrane components, and regulates synaptic assembly at the NMJ 2. Pathogenic mutations in AGRN cause congenital myasthenic syndrome type 8 (CMS8), a rare neuromuscular disorder characterized by proximal limb weakness, ptosis, and impaired neuromuscular transmission detectable by repetitive nerve stimulation 3. CMS8 patients with AGRN mutations demonstrate variable disease progression, with approximately 25% requiring intensive care unit admission, though most respond favorably to adrenergic agents like ephedrine and pseudoephedrine 2. Beyond neuromuscular function, AGRN participates in heparan sulfate biosynthesis regulation and endocytic processes, as demonstrated by its role in influenza virus internalization 4. Recent evidence also implicates AGRN in extracellular matrix homeostasis during cartilage regeneration and as a prognostic biomarker in colorectal cancer 56.