Recent Advances in Protein Tyrosine Sulfation and Its Emerging Roles in Human Diseases

Protein tyrosine sulfation (PTS), an important post-translational modification (PTM), has garnered increasing attention in life sciences in recent years. Following classical and emerging PTMs such as phosphorylation, lactylation, acetylation, and palmitoylation, PTS has now emerged as a novel entry point in disease mechanistic studies. As an evolutionarily conserved modification ubiquitously present in organisms, PTS acts as a core molecular switch that modulates fundamental biological processes via specific conjugation of sulfate groups to tyrosine residues of target proteins. Accumulating evidence has revealed that PTS modifies numerous pivotal functional proteins, such as chemokine receptors, histones, and coagulation factors, and participates in multiple physiological and pathological events, including hormonal modulation, gene transcription, hemostasis, inflammatory responses, cancer progression, and viral infection. Consequently, deeper insight into the mechanisms of PTS and its targeted intervention holds promise for novel therapeutic strategies for related diseases. Nevertheless, the molecular regulatory network of PTS remains poorly understood, which is largely attributed to the limitations of current techniques for the efficient preparation and accurate detection of PTS-modified proteins. This review systematically summarizes the latest advances in the biological functions and regulatory mechanisms of PTS, aiming to provide a theoretical reference for subsequent fundamental research and offer potential therapeutic targets for the clinical treatment of PTS-related diseases.