Post‐translational Modifications in Proteins: Prediction Methods, Biological Functions, and Diseases

Posttranslational modifications (PTMs) act as rapid, reversible switches that reshape protein activity, stability, and interactome, thereby governing virtually every physiological cue from signal transduction to epigenetic memory. Mass spectrometry-based proteomics has considerably extended our knowledge about the occurrence and dynamics of PTMs. Pinpointing disease- or physiology-specific PTM sites remains an open challenge. As a biological process with well-defined stage-specific markers and a precise endpoint, erythropoiesis is orchestrated by the complex interplay of multiple PTM-regulatory networks, making it an ideal model for dissecting the spatiotemporal dynamics, quantitative thresholds, and crosstalk of PTMs. This review delineates the applications, detection, and prediction technologies of PTMs, with an emphasis on the mechanisms of phosphorylation, ubiquitination, methylation, SUMOylation, glycosylation, and acetylation in both physiological and pathological processes. Dissecting PTM circuitry driving erythroid specification and maturation, we show how its perturbation triggers disease, clarifying PTM roles. Additionally, we have investigated the progress made in the clinical translation and drug development of the PTMs field, emphasizing the potential of PTMs in the field of precision medicine as well as the existing challenges. This review aims to provide new insights and perspectives for the study of PTMs.