Protein palmitoylation is a post‑translational lipid modification in which the fatty acid palmitate is covalently attached to specific amino acid residues on proteins, most commonly cysteines via thioester bonds in so‑called S‑palmitoylation. This modification increases protein hydrophobicity and strongly promotes association with cellular membranes, particularly specific microdomains such as lipid rafts. There are several chemical forms of palmitoylation, including S‑, N‑, and O‑palmitoylation, distinguished by whether palmitate is linked through thioester, amide, or oxyester bonds, respectively. S‑palmitoylation of cysteine side chains is the predominant and best‑characterized form in signaling proteins and is labile to hydroxylamine, whereas N‑palmitoylation at N‑terminal residues forms stable amide linkages and is not readily reversible. The reversibility of S‑palmitoylation underlies its role as a regulatory “switch” analogous in concept to phosphorylation or ubiquitination, enabling proteins to shuttle between membrane compartments and the cytosol according to cellular cues. AkrivisBio’s Palmitoylated Protein Assay is a simple, sensitive protocol for attaching palmitate to proteins within active cells and subsequently labeling them to allow for detection.
