Dipeptidyl-peptidase-like protein 6 (DPPX) antibody-associated encephalitis, mediated by DPPX antibodies in serum and/or cerebrospinal fluid, is a novel autoimmune encephalitis. It presents with multifocal and diverse neurological disorders characterized by the triad of prodromal weight loss and/or gastrointestinal symptoms (diarrhea predominately), cognitive-mental dysfunction, and central nervous system hyperexcitability. Brain magnetic resonance imaging shows non-specific abnormalities. Immunotherapy can result in clinical improvements, but the disease is prone to relapse.