Pseudoenzymes: dead enzymes with a lively role in biology

This Special Issue comprises twelve authoritative reviews that highlight an understudied but rapidly developing area of biology: catalytically inactive enzyme homologs. These pseudoenzymes, sometimes called 'dead enzymes', are found within most enzyme families and generally arose via gene duplication events. Dead enzymes have lost their enzymatic capacity, often via the evolutionary loss of key catalytic residues. However, as this Special Issue highlights, pseudoenzymes are far from being functionally 'dead'. In fact, they fulfill a range of critical biochemical roles, frequently appearing more versatile as biochemical regulators than their catalytic cousins. The functions of dead enzymes from diverse enzyme families often follow recurring themes, including allosteric regulation of their catalytically active counterparts, acting as signaling scaffolds, or as inhibitors that recognize and sequester the substrates of their catalytic homologs. As well as highlighting the breadth and depth of dead enzyme biology, this Special Issue emphasizes the power of pseudoenzymes as key biochemical regulators in health and disease and potentially as more tractable drug targets than some enzymes themselves. We hope you find these reviews enlivening, and we thank the authors for these excellent contributions.