**Preface to "Ubiquitination in Health and Diseases"**

Dear Colleagues,

Ubiquitination is a representative, reversible biological process for the post-translational modification of various proteins with multiple catalytic sequences, including ubiquitin itself, the E1 ubiquitin-activating enzymes, the E2 ubiquitin-conjugating enzymes, and the E3 ubiquitin ligase and deubiquitinating enzymes. Since the ubiquitin–proteasome system plays a pivotal role in various molecular life phenomena such as cell cycle control, protein quality control, and cell surface expression of ion transporters, its failure causes various diseases such as cancer, neurodegenerative diseases, cardiovascular diseases, and hypertension. Various genetic diseases derived from abnormalities in genes involved in ubiquitination have been reported, such as Parkinsonism, Cushing disease, and Liddle syndrome. Ubiquitination is a post-translational modification of proteins subsequent to phosphorylation, and approximately 40% of the proteins encoded by human genes undergo this modification. Although clinical applications targeting ubiquitination are still limited compared with those directed to kinase systems such as tyrosine kinases, for which an inventory of tyrosine kinase inhibitors is already available in clinical settings, many compounds affecting ubiquitination and presenting high pharmacological activity have been identified at the basic research level; therefore, future developments can be expected. Abnormalities of E3 ubiquitin ligase affect the phenotypes specific to each target substrate, which, thus, are also attractive targets for selective drug discovery. In this Special Issue of the *International Journal of Molecular Science*, we would like to invite your contributions in the form of either original research articles or reviews, in the expanding field of mechanic, functional, and pharmacological dissections, concerning the physiological and pathological implications of specific ubiquitination reactions.

> **Tomoaki Ishigami** *Editor*
