Fruit ripening is a highly coordinated developmental process that transforms immature fruits into edible organs adapted for seed dispersal and human consumption. Although transcriptional regulation has long been acknowledged as a fundamental mechanism underlying ripening control, accumulating evidence now indicates that post-translational modifications (PTMs) function as master regulatory switches that precisely control protein activity, stability, and interactions. PTMs such as phosphorylation, ubiquitination, acetylation, redox modifications, and methylation establish dynamic regulatory networks that integrate hormonal signals, metabolic fluxes, and environmental signals to control the complex biochemical and physiological changes during fruit ripening. This review summarizes current understanding of PTM-mediated regulation in both climacteric and nonclimacteric fruits, emphasizing how modification cascades control key processes including ethylene signaling, cell wall remodeling, pigment accumulation, and stress responses. We explore emerging crosstalk networks in which multiple PTMs target important proteins to form complex molecular switches and discuss recent methodological advances that facilitate systems-level analysis of PTM. Integrating PTM research with precision agriculture and biotechnology offers promising approaches for improving fruit quality, extending shelf-life, and enhancing stress tolerance in the context of global climate change.

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