Proteome-Scale Analysis of Protein S-Acylation Comes of Age

Protein S -acylation (commonly known as palmitoylation) is a widespread reversible lipid modification, which plays critical roles in regulating protein localization, activity, stability, and complex formation. The deregulation of protein S -acylation contributes to many diseases such as cancer and neurodegenerative disorders. The past decade has witnessed substantial progress in proteomic analysis of protein S -acylation, which significantly advanced our understanding of S -acylation biology. In this review, we summarized the techniques for the enrichment of S -acylated proteins or peptides, critically reviewed proteomic studies of protein S -acylation at eight different levels, and proposed major challenges for the S -acylproteomics field. In summary, proteome-scale analysis of protein S -acylation comes of age and will play increasingly important roles in discovering new disease mechanisms, biomarkers, and therapeutic targets.