Targeting pantothenate kinases in human diseases: Biochemistry and pharmacotherapy

Pantothenate kinases (PANKs), which regulate the first and rate-limiting step of coenzyme A (CoA) biosynthesis, have emerged as therapeutic targets for various human diseases. PANKs family consists of PANK1, PANK2, PANK3, and PANK4. We summarized the research progress of the PANK family in the last two decades. Notably, PANKs play critical roles in diverse pathophysiological mechanisms underlying human diseases, including pantothenate kinase-associated neurodegeneration (PKAN), propionic acidemia (PA), lipid metabolic disorders, Parkinson's disease (PD), glioma, clear cell renal cell carcinoma (ccRCC), and insulin resistance (IR). Nevertheless, the precise relationship between PANKs and human diseases remained ambiguous. Therefore, this review provides a comprehensive summary of the structural properties, molecular mechanisms, and relevant modulators that govern PANK activity. In conclusion, targeting PANKs as regulators of CoA biosynthesis and disease pathogenesis contributes to connecting biochemistry with pharmacotherapy.