Recent Overview of Protein Palmitoylation and Profiling Methodologies

Protein palmitoylation is a reversible posttranslational modification in which a palmitoyl group (a 16-carbon saturated fatty acid) is covalently attached to cysteine residues on proteins, typically through a thioester bond. This modification affects the protein's hydrophobicity, influencing its membrane association, localization, stability, trafficking, and overall function. Dysregulation of palmitoylation has been implicated in diseases such as cancer, neurodegenerative diseases, and cardiovascular disorders. In this review, we summarize the recent findings related to protein palmitoylation and its biological functions. More importantly, we examine proteomic studies that utilize active-based protein profiling (ABPP) to design novel probes or inhibitors aimed at enhancing the accuracy and efficiency of large-scale analyses of protein palmitoylation. These advancements will facilitate the findings of novel therapeutic targets and the designing of targeted therapies, providing increasingly critical insights into the role of this modification in health and diseases.