COASY (coenzyme A synthase) is a bifunctional enzyme catalyzing the final two steps of coenzyme A (CoA) biosynthesis: adenylation of 4'-phosphopantetheine and phosphorylation of dephospho-CoA to CoA 1. CoA is essential for multiple metabolic pathways including the tricarboxylic acid cycle, lipid synthesis, histone acetylation, and heme biosynthesis 1. COASY expression is upregulated during erythroid differentiation and is critical for heme accumulation and proper erythropoiesis 2. COASY mutations cause neurodegeneration with brain iron accumulation 6 (NBIA-VI) and pontocerebellar hypoplasia 12, accounting for ultrarare NBIA cases 3. Zebrafish studies demonstrate that COASY loss reduces CoA content, impairs dorso-ventral patterning through decreased bone morphogenetic protein signaling, and increases cell death during neural and vascular development 4. Beyond neurodegeneration, COASY dysfunction contributes to metabolic dysfunction-associated steatohepatitis (MASH) pathogenesis; COASY knockdown reduces cholesterol accumulation in liver lipid droplets and prevents MASH and fibrosis development 56. Additionally, elevated COASY expression is associated with lung adenocarcinoma progression through mitophagy-related mechanisms 7. COASY promoter methylation shows diagnostic potential as a biomarker for Alzheimer's disease and amnestic mild cognitive impairment, with 96.6% sensitivity and 96.7% specificity 8.