70 Years of Polyphosphate Kinase: Expanding Functions and Emerging Design Considerations

Polyphosphate kinases (PPKs) have long served as practical tools for ATP regeneration. Recent reports demonstrating broader nucleotide specificity have renewed interest in this enzyme family and expanded its perceived functional scope. At the same time, several recurring challenges have become more apparent, including ambiguity in classification, the frequent need for stability optimization, and the accumulation of phosphate by-products in coupled systems. These aspects do not represent insurmountable obstacles, but they influence how PPKs are compared, engineered, and integrated into catalytic platforms. This perspective argues that clearer functional annotation and early consideration of structural and process-level parameters can improve the interpretability and application potential of PPK-based systems.