Schizoaffective disorder (SAD) is a severe psychiatric condition characterized by the coexistence of psychotic symptoms and mood episodes. Growing evidence suggests that immune dysregulation and inflammatory processes contribute to the pathophysiology of schizophrenia-spectrum disorders, including SAD. α-N-acetylgalactosaminidase is a lysosomal enzyme involved in glycoprotein metabolism and immune regulation through its effects on Gc protein-derived macrophage activating factor. Previous studies have reported altered α-N-acetylgalactosaminidase levels in schizophrenia and bipolar disorder; however, its role in SAD has not been investigated. The aim of this cross-sectional study is to compare serum α-N-acetylgalactosaminidase levels among patients with SAD during acute exacerbation and remission phases and healthy controls. The study also examines the relationships between α-N-acetylgalactosaminidase levels, symptom severity, and systemic inflammation. Clinical assessments include the Positive and Negative Syndrome Scale, Young Mania Rating Scale, Beck Depression Inventory, and Global Assessment Scale. Systemic inflammation is evaluated using the Aggregate Index of Systemic Inflammation, derived from routine complete blood count parameters. By investigating the association of α-N-acetylgalactosaminidase with clinical and inflammatory features of SAD, this study seeks to improve understanding of the biological mechanisms underlying the disorder and to explore the potential utility of α-N-acetylgalactosaminidase as a biomarker related to disease state and symptom severity.