**4. Protein post-translational modifications (PTMs)**

In general, various protein post-translational modifications (PTMs) increase the functional diversity of the proteome through adding covalent functional groups, proteolytically cleaving regulatory subunits, or degrading the entire protein. These covalent modifications of proteins involving in phosphorylation, glycosylation, ubiquitination, nitrosylation, methylation, acetylation, lipidation, and proteolysis have affected all the details of cellular physiology and pathology. The post-translational modifications of proteins further contribute to the biological complexity from genome to proteome. PTMs play an important role in regulating activity, localization, and interaction with cellular molecules (such as proteins, nucleic acids, lipids, and cofactors) [38, 39].

Therefore, better understanding and analysis of protein post-translational modifications may be crucial for the study of cell biology, disease treatment and disease prevention including cardiovascular diseases, several forms of cancers, neurodegenerative diseases and diabetes, etc. [40].

#### **4.1 Post-translational modifications of occludin**

In recent years, post-translational modifications of occludin, as representative tight junction proteins, have become a research hotspot. The reported post-translational modifications of occludin include proteolysis, phosphorylation, and ubiquitination, which have all been shown to play vital roles in the course of disease occurrence, development, and convalescence [41, 42].
