14-3-3 protein zeta/delta (14-3-3ζ) is a protein that in humans is encoded by the YWHAZ gene on chromosome 8. The protein encoded by this gene is a member of the 14-3-3 protein family and a central hub protein for many signal transduction pathways. 14-3-3ζ is a major regulator of apoptotic pathways critical to cell survival and plays a key role in a number of cancers and neurodegenerative diseases. As a major hub protein, 14-3-3ζ is involved in various diseases and disorders. For one, 14-3-3ζ plays a central role in cell proliferation and, by extension, tumor progression. The protein has been implicated in many cancers, including lung cancer, breast cancer, lymphoma, and head and neck cancer, through pathways such as mTOR, Akt, and glucose receptor trafficking. Notably, it has been associated with chemoresistance and, thus, is a promising therapeutic target for cancer treatment. So far, it stands to become a prognostic marker for breast cancer, lung cancer, head and neck cancer, and possibly gastric cancer in patients who might require more aggressive treatment. In addition to cancers, 14-3-3ζ has been implicated in pathogenic infections and neurodegenerative diseases, including Creutzfeldt–Jakob disease, Parkinson’s disease, and Alzheimer’s disease (AD). 14-3-3ζ has been observed to participate in AD through its interaction with tau protein, and its expression is correlated with disease severity.