PANK4 (pantothenate kinase 4) is a bifunctional enzyme that, despite its name, lacks traditional pantothenate kinase activity in humans due to evolutionary mutations that inactivated its kinase domain 1. Instead, human PANK4 functions primarily as a phosphatase with specificity for 4'-phosphopantetheine and its oxidatively damaged forms, serving as a protective mechanism in coenzyme A (CoA) biosynthesis 2. The enzyme hydrolyzes excess 4'-phosphopantetheine to prevent oxidative damage and removes damaged forms like sulfonate derivatives that could generate inactive CoA 2. PANK4 plays crucial regulatory roles in cellular metabolism by controlling acetyl-CoA levels in skeletal muscle, where muscle-specific deletion impairs fatty acid oxidation and glucose metabolism 3. In immune responses, PANK4 regulates CD4+ T-cell proliferation through modulation of de novo lipid synthesis and is negatively regulated by CD28-PI3K signaling 4. The enzyme also influences cancer therapy resistance, with elevated expression associated with temozolomide resistance in glioblastoma through modulation of cellular detoxification pathways 5 and contributing to histone acetyltransferase inhibitor resistance by affecting acetyl-CoA levels 6. Clinically, PANK4 mutations are associated with cataract formation 7.