Protein lipidation, the attachment of lipids onto proteins, is a posttranslational modification that modulates the function of the targeted proteins. These lipid modifications increase protein hydrophobicity and can affect the folding, stability, localization, interaction with other proteins, and association with specific membrane domains. Proteins can be covalently modified by different types of lipids including phospholipids, isoprenoids, fatty acids, cholesterol, GPI (glycosylphosphatidylinositol)-anchors, and LDEs (lipid-derived electrophiles). S-palmitoylation or S-acylation is a reversible form of lipidation in which the fatty acid palmitate is attached to specific cysteine residues by a labile thioester bond. Mis-regulation of lipid metabolism and protein lipidation has been linked to pathological conditions, but the molecular mechanisms involved, and how it affects protein lipidation levels remains elusive. In part this is due to the paucity of information about how lipidation and the enzymes that regulate it are controlled by signaling pathways in the cell. In this research topic we aim to describe the importance of protein lipidation for the function of the targeted proteins, and how alterations in these post-translational modifications are connected to human diseases and the development of novel therapeutic approaches.

The functions of protein lipidation in cellular physiology and how its alterations affect human health are still under study. One impediment in the development of this field has been the limited methods available to study protein lipidation and the complexity of cellular lipids. Besides, while some types of protein lipidation such as S-palmitoylation have received wide attention in the last years, others, such as N-palmitoylation are mainly unknown. Therapeutical approaches targeting lipidation have been explored for cancer treatment purposes but essentially uninvestigated for other diseases. Advancement of lipidomics in recent years might help to shed light on how lipid dynamics affect protein lipidation in health and disease.

The scope of the Research Topic is to gather the latest information about the following themes:

- Diversity of protein lipidation, including rare or lesser-known forms of protein lipidation.
- Involvement of protein lipidation in the function and localization of the targeted proteins, and in cellular physiology.
- Regulatory pathways of lipidating and de-lipidating enzymes.
- S-palmitoylation as a reversible form of protein lipidation.
- Crosstalk between lipidation and other post-translational modifications.
- Interconnections between lipid metabolism and protein lipidation.
- Implications of the alterations in protein lipidation in the pathophysiology of human diseases.
- Targeting lipidation for the development of novel therapeutic approaches to combat human diseases.
- Current methods and experimental tools to detect, quantify and manipulate protein lipidation and cellular lipids, their limitations, and contributions to the knowledge of protein lipidation functions and pathological relevance

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