Engineered Protein Modification: A New Paradigm for Enhancing Biosensing Sensitivity and Diagnostic Accuracy

Protein modifications, particularly post-translational modifications (PTMs) such as phosphorylation and glycosylation, are fundamental mechanisms regulating cellular activity and disease pathogenesis, with their detection emerging as a promising frontier for advanced diagnostics. This review systematically examines the integration of engineered protein modifications with biosensing technologies to enhance analytical performance and diagnostic accuracy. Through critical analysis of current methodologies, we highlight how strategic manipulation of PTMs improves biosensor sensitivity and specificity in applications ranging from early disease detection to environmental monitoring. The analysis identifies significant advancements in detection platforms while acknowledging persistent challenges in real-world integration and standardization. We conclude that optimizing protein modification-based sensing strategies represents a crucial pathway for developing robust, clinically translatable diagnostic tools, and propose focused research directions to address existing technical barriers and accelerate practical implementation.