PANK1 catalyzes the phosphorylation of pantothenate (vitamin B5) to 4'-phosphopantothenate, the rate-limiting step in coenzyme A (CoA) biosynthesis. CoA is an essential cofactor for the tricarboxylic acid cycle, fatty acid oxidation, histone acetylation, and synthesis of lipids, glycans, and heme 1. PANK1 is regulated by multiple cellular signals including p53, which directly activates PANK1 transcription in response to DNA damage and metabolic stress 23. The protein exists as two isoforms with distinct regulatory properties; the longer isoform undergoes feedback inhibition by CoA and acyl-CoA species, allowing cells to modulate CoA production based on metabolic demand. PANK1 has emerged as a therapeutic target in heart failure: sodium-glucose cotransporter-2 inhibitors (SGLT2i), medications approved for heart failure treatment, directly activate PANK1 at physiological concentrations, promoting CoA synthesis and enhancing fuel utilization in failing hearts 4. In cancer, PANK1 expression is downregulated in glioma and correlates with better prognosis 5, while in hepatocellular carcinoma, PANK1 inhibits Wnt/β-catenin signaling through cooperation with casein kinase 1α 6. Genetic variation in PANK1 is associated with asthma exacerbations and insulin homeostasis 78. Recent evidence suggests circular RNA derived from PANK1 may promote dopaminergic neurodegeneration in Parkinson's disease models 9.