• Over 30 types of lysine PTMs have been characterized, with about 300,000 modification sites identified, highlighting their extensive regulatory roles.
• Mass spectrometry combined with antibody-based enrichment has been pivotal in advancing the global characterization of lysine PTMs.
• Crosstalk between different lysine PTMs on histones and non-histone proteins adds complexity to gene regulation and disease mechanisms.
• Targeting lysine PTM regulatory enzymes (writers, erasers, readers) presents a promising therapeutic strategy for various diseases.