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Background: Anti-N-methyl d-aspartate (NMDA) receptor encephalitis is an autoimmune encephalitis characterized by neuronal surface antibodies targeting NMDA receptor in the spinal fluid and serum. After acute disseminated encephalomyelitis, anti-NMDA receptor encephalitis is the most frequent cause of autoimmune encephalitis. Despite its clinical significance, the exact prevalence and optimal treatment strategies for this condition remain poorly understood. This comprehensive review aims to evaluate the therapeutic potential of bortezomib as a novel therapy for anti-NMDA receptor encephalitis in hopes of mitigating symptoms and improving outcomes for anti-NMDA receptor encephalitis patients. Results: The disease is primarily triggered by immunoreactivity against the NMDA receptor 1 (NR1). Recurrence rates are of significant concern in the treatment of anti-NMDA receptor encephalitis, given that a substantial portion of patients are unresponsive to immunosuppressive and immunomodulatory therapies. Thus, the exploration of alternative therapies is necessary. In recent years, bortezomib, a proteasome inhibitor, has emerged as a potential therapeutic candidate by inhibiting autoantibody production against NMDA receptor. Bortezomib exerts immunosuppressive and immunomodulatory effects by inhibiting the production of autoantibodies against NMDA receptor. Studies suggest that bortezomib, by inhibiting proteasome activity and altering antigen presentation, can suppress autoantibody production and immune cell activation, contributing to clinical improvement. However, literature reviews on the utilization of bortezomib in the context of anti-NMDA receptor encephalitis are still highly limited. Conclusions: Bortezomib presents a promising avenue for intervention. While initial studies suggest its potential to modify the immune response and alleviate symptoms, further comprehensive investigations are imperative to establish optimal dosing, usage guidelines, and long-term safety profiles. [ABSTRACT FROM AUTHOR]