ACOD1 (aconitate decarboxylase 1) is a mitochondrial enzyme that catalyzes the production of itaconate from cis-aconitate, serving as a key regulator of immunometabolism and inflammation 1. The enzyme is highly upregulated in activated immune cells, particularly macrophages and neutrophils, in response to inflammatory stimuli including LPS, cytokines, and pathogen-associated molecular patterns 1. ACOD1-derived itaconate functions as an anti-inflammatory metabolite through multiple mechanisms: it alkylates cysteine residues on KEAP1, leading to Nrf2 activation and enhanced anti-oxidant/anti-inflammatory gene expression 2; inhibits succinate dehydrogenase activity, limiting glycolysis and ROS production 3; and provides cellular protection against ferroptosis 4. The enzyme plays crucial roles in antimicrobial defense by enabling macrophages to generate itaconate for pathogen inhibition, while also serving as a negative feedback regulator to prevent excessive inflammation 5. In disease contexts, ACOD1 has dual roles: it protects against inflammatory diseases and supports glucocorticoid anti-inflammatory effects 6, but can also contribute to tumor immune evasion and metastasis by conferring ferroptosis resistance to cancer-associated immune cells 47. These diverse functions establish ACOD1 as a critical immunometabolic checkpoint with significant therapeutic potential.