Editorial: Protein lipidation in health and disease

Editorial on the Research Topic Protein lipidation in health and diseaseProtein lipidation, the attachment of lipids to proteins, influences how proteins fold, their stability, trafficking, interaction with other proteins, and association with specific domains on cellular membranes.Various types of lipids, such as phospholipids, isoprenoids, fatty acids, cholesterol, GPI (glycosylphosphatidylinositol)-anchors, and LDEs (lipid-derived electrophiles), modify proteins covalently.S-palmitoylation or S-acylation is a reversible type of lipidation where a fatty acid called palmitate attaches to specific cysteine residues through a labile thioester bond.N-palmitoylation (via a stable amine bond) and O-palmitoylation (via a stable ester bond) are less common and irreversible kinds of palmitoylation (Chen et al., 2018).S-palmitoylation (called palmitoylation for simplicity in this editorial) is catalysed in mammals by a family of 23-24 proteins called palmitoyl acyltransferases (zDHHC-PATs), and de-acylation is mediated by α/β serine hydrolases and thioesterases, including APT1 (acyl-protein thiosterase 1) and ABHD17 thioesterases, among others (Zhou et al., 2023).Additionally, several PAT-interacting proteins have been identified that regulate their function and localization (Salaun et al., 2020).The objective of this Research Topic is to compile the most recent insights on the impact of protein lipidation on protein function and explore how alterations in these modifications are linked to the pathophysiology of human diseases, paving the way for the development of novel therapeutic strategies.One important feature of many post-translational modifications (PTMs) is how they can be regulated by gene-splicing variants.For example, the splice variant of the AMPA scaffolding protein GRIP1, GRIP1b, can be palmitoylated, whereas GRIP1a cannot, affecting its subcellular distribution (Hanley and Henley, 2010).In this line, Wirth and Ponimaskin review the literature describing that the small GTPase Cdc42 splice variant which is palmitoylated (Cdc42-palm) is mainly expressed in the brain, in contrast to its prenylated ubiquitous form (Cdc42-prenyl).It would be interesting to further explore in the future whether these are anecdotal cases or whether the regulation of splice variants and protein isoforms are more widespread modulators of protein palmitoylation.Recent studies have revealed that numerous immune-associated proteins undergo S-palmitoylation.These findings have shed light on the vital roles played by palmitoylation in immune function, particularly in directing immune signalling proteins to the membrane and lipid rafts.