HAAO (3-hydroxyanthranilate 3,4-dioxygenase) catalyzes the oxidative ring opening of 3-hydroxyanthranilate to form 2-amino-3-carboxymuconate semialdehyde, which spontaneously cyclizes to quinolinate 1. This enzyme functions as a critical step in the kynurenine pathway, which synthesizes NAD+ de novo from tryptophan 1. HAAO consumes 3-hydroxyanthranilic acid (3-HA), a tryptophan metabolite that acts as a potent antioxidant; by depleting 3-HA, HAAO inhibits its ferroptosis-protective effects in cancer cells, and its expression correlates with lipid peroxidation and poor clinical outcomes 2. HAAO is also regulated by transcription factors HNF4A and HNF1A in pancreatic beta cells, with potential roles in beta cell function 3. HAAO is associated with congenital NAD deficiency disorder (CNDD), characterized by vertebral, cardiac, renal, and limb defects; biallelic loss-of-function variants in HAAO cause severe NAD deficiency during gestation, which niacin supplementation can prevent 14. Additionally, HAAO expression is downregulated in particulate matter-exposed macrophages during chr2 obstructive pulmonary disease pathogenesis, contributing to impaired NAD+-dependent histone deacetylation and pro-inflammatory activation 5. HAAO also participates in 3-HA degradation pathways affecting cognitive function, as altered HAAO expression in response to microbiota changes influences attention in obesity 6.