Neurodegenerative diseases, characterized by the progressive loss of neuronal function, are increasingly linked to intricate cellular and molecular mechanisms. Among these, astrocytes, essential glial cells in the central nervous system (CNS), and necrotic pathways have emerged as pivotal players in disease progression. Anti-IgLON5 disease, a unique neurodegenerative disorder with both autoimmune and tauopathy features, provides a novel context to examine these interactions. This article explores the role of necrosis and astrocyte dysfunction in the pathophysiology of anti-IgLON5 disease, shedding light on broader implications for neurodegenerative diseases. Insights into these mechanisms could pave the way for innovative therapeutic strategies targeting glial cells and necrotic processes.