The role of the 14-3-3 protein family in health, disease, and drug development

•A thorough review of 14-3-3 protein function.•Discussion of 14-3-3 proteins in health, disease, and animal models.•Review of 14-3-3 protein-targeted compounds, advantages and disadvantages of each.•Future work in drug discovery targeting 14-3-3 proteins. 14-3-3 proteins regulate intracellular signaling pathways, such as signal transduction, protein trafficking, cell cycle, and apoptosis. In addition to the ubiquitous roles of 14-3-3 isoforms, unique tissue-specific functions are also described for each isoform. Owing to their role in regulating cell cycle, protein trafficking, and steroidogenesis, 14-3-3 proteins are prevalent in human diseases, such as cancer, neurodegeneration, and reproductive disorders, and, therefore, serve as valuable drug targets. In this review, we summarize the role of 14-3-3 proteins in normal and disease states, with a focus on 14-3-3γ and ɛ. We also discuss drug compounds targeting 14-3-3 proteins and their potential therapeutic uses.