Pyrimidine biosynthetic enzyme CAD: Its function, regulation, and diagnostic potential

CAD (Carbamoyl-phosphate synthetase 2, Aspartate transcarbamoylase, and Dihydrooro-tase) is a multifunctional protein that participates in the initial three speed-limiting steps of pyrimi-dine nucleotide synthesis. Over the past two decades, extensive investigations have been conducted to unmask CAD as a central player for the synthesis of nucleic acids, active intermediates, and cell membranes. Meanwhile, the important role of CAD in various physiopathological processes has also been emphasized. Deregulation of CAD-related pathways or CAD mutations cause cancer, neurological disorders, and inherited metabolic diseases. Here, we review the structure, function, and regulation of CAD in mammalian physiology as well as human diseases, and provide insights into the potential to target CAD in future clinical applications.