PANK3 (pantothenate kinase 3) catalyzes the phosphorylation of pantothenate to 4'-phosphopantothenate, the first and rate-limiting step of coenzyme A (CoA) biosynthesis 1. PANK3 is the most highly expressed pantothenate kinase isoform in humans 2. The enzyme functions as a homodimer with allosterically coupled active sites that coordinately switch between active and inactive conformations 3. ATP binding induces a conformational change in the amino-terminal nucleotide binding domain to close the active site, while acetyl-CoA provides feedback inhibition, making PANK3 the master regulator of CoA biosynthesis 3. Subcellular fractionation studies demonstrate PANK3 is predominantly cytosolic with broad expression across cell types 2. PANK3 has emerged as a therapeutic target because modulating its activity can affect sensitivity to histone acetyltransferase inhibitors by controlling acetyl-CoA availability 4. Disease relevance includes roles in pantothenate kinase-associated neurodegeneration (PKAN), lipid metabolic disorders, Parkinson's disease, cancer, and insulin resistance 5. Additionally, PANK3 genetic variation associates with brain iron homeostasis, implicating CoA metabolism in neurodegeneration pathways 6.