IGLON5 (IgLON family member 5) is a cell adhesion molecule mediating heterophilic cell-cell adhesion and synapse assembly regulation [GO Annotations]. The protein is located on the plasma membrane and functions as a neuronal surface antigen. IGLON5's primary clinical significance derives from its role in autoimmune encephalitis: anti-IgLON5 disease is a recently characterized autoimmune disorder where autoantibodies against IGLON5 cause neuronal damage 1. Unlike other autoimmune encephalitis-related antibodies, anti-IgLON5 antibody-induced neuronal damage is irreversible, linking autoimmunity with neurodegeneration 1. The disease presents with distinctive sleep disorders alongside heterogeneous neurological symptoms including cognitive dysfunction, psychiatric manifestations, and atypical presentations mimicking progressive supranuclear palsy or motor neuron disease 2. Neuropathological examination reveals a novel tauopathy preferentially affecting the hypothalamus and brainstem tegmentum 1. Genetic studies have identified human leukocyte antigen (HLA) associations with anti-IgLON5 disease 3. MRI findings are often unremarkable, though brainstem, hippocampal, and cerebellar lesions and atrophy may occur in some cases 4. Early diagnosis requires comprehensive neural antibody testing using both tissue and cell-based assays 5, with neurofilament light chain levels emerging as a potential biomarker for immunotherapy response 2.