KYNU (kynureninase) is a pyridoxal phosphate-dependent enzyme that catalyzes the conversion of L-kynurenine and L-3-hydroxykynurenine into anthranilic acid and 3-hydroxyanthranilic acid (3-HAA), respectively, with preference for the L-3-hydroxy form 1. As a key enzyme in the kynurenine pathway, KYNU participates in de novo NAD+ biosynthesis from tryptophan 12. Beyond its canonical metabolic role, KYNU functions as a radical-trapping antioxidant through 3-HAA production, protecting cells from ferroptotic death in cancer contexts 3. KYNU expression is upregulated by CD44 signaling in breast cancer and associates with tumor cell invasion and metastasis 4. In the tumor microenvironment, KYNU modulates macrophage polarization and promotes stemness remodeling through SOD2-dependent mitochondrial ROS regulation and endoplasmic reticulum stress responses 56. Pathogenic variants in KYNU cause NAD deficiency leading to congenital malformations including cardiac, vertebral, and renal defects; niacin supplementation prevents these defects 1. KYNU also functions protectively in acute kidney injury through caloric restriction-dependent NAD+ synthesis 2. Clinically, KYNU dysregulation is implicated in multiple malignancies and obesity-associated asthma, positioning it as a potential therapeutic target 78.