Large-scale genome-wide association studies have identified hundreds of multiple sclerosis risk loci, most of which implicate immune pathways and establish multiple sclerosis as a highly polygenic, immune-mediated disease. These findings help explain why immune-modifying therapies suppress relapses and new lesion formation. However, susceptibility genetics does not adequately explain disability accumulation, variation in disease course, or treatment response. Evidence from rare-variant studies, genetic studies of disease severity and disability progression, epigenetic analyses, gene-environment studies, and Epstein-Barr virus research is beginning to extend this genetic framework from susceptibility to disease expression. Still, the direct clinical relevance of this research remains constrained by modest individual-level predictive value, underpowered studies of genetic determinants of disease severity and disability progression, complex regulatory mechanisms linking variants to function, and restricted generalisability across populations. At present, multiple sclerosis genetics is most useful for interpreting mechanisms, prioritising therapeutic targets, supporting causal inference, informing biomarker discovery, and enriching research cohorts. Future clinical value will likely depend on integrating genetic architecture with longitudinal clinical, imaging, biomarker, and multi-omic data to identify the contexts in which prevention or treatment is most likely to succeed.

The discovery of antibody-mediated glial and neuronal disorders has transformed the diagnosis and treatment of neurological diseases previously considered idiopathic or not recognised as immune-mediated. Antibody-mediated disorders targeting glial aquaporin-4 and myelin oligodendrocyte glycoprotein are distinct nosological entities, defined by specific targets, mechanisms, syndromes, and therapeutic implications. By contrast, antibody-mediated disorders targeting neuronal antigens (ie, autoimmune encephalitides) are still frequently analysed collectively, with data from different disorders pooled as if they represent a single disease rather than distinct entities. Evidence from anti-NMDA receptor encephalitis, anti-LGI1 encephalitis, and anti-IgLON5 disease (used here as exemplars of autoimmune encephalitides) indicates that individual autoimmune encephalitides differ in demographics, triggers, mechanisms, clinical manifestations, post-acute trajectories, and treatment requirements. The broad, heterogeneous presentations of autoimmune encephalitides require coordinated multidisciplinary care within and beyond neurology, involving specialists in paediatrics, infectious diseases, epilepsy, movement disorders, sleep medicine, intensive care, cognitive rehabilitation, and other relevant disciplines. Such interdisciplinary collaboration facilitates the recognition of new diseases and elucidation of the causes of previously unclassified disorders. Improving patient care requires not only aetiological and mechanistic insight to enable development of targeted therapies but also strengthened cross-specialty expertise to optimise diagnosis and management.