The Nuclear Casein and Cyclin-dependent Kinase Substrate 1 (NUCKS1) protein is highly conserved in vertebrates, predominantly localized to the nucleus and one of the most heavily modified proteins in the human proteome. NUCKS1 expression is high in stem cells and the brain, developmentally regulated in mice and associated with several diverse malignancies in humans, including cancer, metabolic syndrome and Parkinson's disease. NUCKS1 function has been linked to modulating chromatin architecture and transcription, DNA repair and cell cycle regulation. In this review, we summarize and discuss the published information on NUCKS1 and highlight the questions that remain to be addressed to better understand the complex biology of this multifaceted protein.

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