The CHRNE antibody targets the epsilon subunit of the nicotinic acetylcholine receptor (AChR), a critical component of the neuromuscular junction (NMJ). AChRs are ligand-gated ion channels composed of five subunits (α2βδε in adults). The ε subunit, encoded by the CHRNE gene, replaces the γ subunit during development, forming mature receptors essential for neuromuscular signal transmission. In autoimmune myasthenia gravis (MG), autoantibodies against AChRs disrupt neuromuscular signaling, causing muscle weakness. While most MG patients have antibodies against the α1 subunit, a subset (≤5%) specifically targets the ε subunit. These anti-CHRNE antibodies impair receptor clustering, reduce synaptic response, and accelerate receptor degradation, leading to fatigable weakness in ocular, bulbar, or limb muscles. Additionally, CHRNE mutations cause congenital myasthenic syndromes (CMS), highlighting the subunit's functional importance. Detection of CHRNE antibodies aids in diagnosing seronegative MG cases and guides immunotherapy strategies. Research continues to explore epitope specificity and clinical correlations of these antibodies.