This Special Issue contains twelve reviews as well as an interview that feature a rapidly developing area of biology: catalytically inactive enzyme homologs, also known as pseudoenzymes. These pseudoenzymes, are often referred to as “dead enzymes”, and are found within most enzyme families. Pseudoenzymes have lost their enzymatic capacity, often via the evolutionary loss of key catalytic residues, however, pseudoenzymes are far from being functionally “dead”, as evidenced within this Special Issue. 

As a matter of fact, pseudoenzymes fulfil a range of integral biochemical roles, frequently appearing more versatile as biochemical regulators than their catalytic cousins. As well as focusing on 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 outstanding contributions to The FEBS Journal.

Pseudoenzymes: dead enzymes with a lively role in biology
Adrain, Colin
https://doi.org/10.1111/febs.15535

In Conversation With Janet Thornton
Dhillon, Paraminder; Thornton, Janet
https://doi.org/10.1111/febs.15567

Challenges in the annotation of pseudoenzymes in databases: the UniProtKB approach
Zaru, Rossana; Magrane, Michele; Orchard, Sandra
https://doi.org/10.1111/febs.15100

Identifying pseudoenzymes using functional annotation. How loss of function correlates with mutations in the catalytic site
Thornton, Janet; Ribeiro, António; Tyzack, Jonathan; Borkakoti, Neera
https://doi.org/10.1111/febs.15142

Enzymes, Pseudoenzymes, and Moonlighting Proteins: Diversity of Function in Protein Superfamilies
Jeffrey, Constance
https://doi.org/10.1111/febs.15446

Cataloguing the dead: breathing new life into pseudokinase research
Eyers, Patrick; Shrestha, Safal; Byrne, Dominic; Harris, John; Kannan, Natarajan
https://doi.org/10.1111/febs.15246

Pseudokinases: a tribble-edged sword
Keeshan, Karen; Richmond, Laura
https://doi.org/10.1111/febs.15096

The PEAK family of Pseudokinases, their role in cell signalling and cancer
Lucet, Isabelle; Patel, Onisha; Roy, Michael; Murphy, James
https://doi.org/10.1111/febs.15087

The dead phosphatases society: a review of the emerging roles of pseudophosphatases
Farhan, Hesso; Reiterer, Veronika; Pawlowski, Krzysztof; Desrochers, Guillaume; Pause, Arnim; Sharpe, Hayley
https://doi.org/10.1111/febs.15431

Pseudophosphatase MK-STYX: the atypical member of the MAP kinase phosphatases
Hinton, Shanta
https://doi.org/10.1111/febs.15426

The pseudoGTPase group of pseudoenzymes
Boggon, Titus; Stiegler, Amy
https://doi.org/10.1111/febs.15554

FLIP(L): a pseudo-caspase
Longley, Daniel; Smyth, Peter; Sessler, Tamas; Scott, Christopher
https://doi.org/10.1111/febs.15260

The complex life of rhomboid pseudoproteases
Adrain, Colin; Cavadas, Miguel
https://doi.org/10.1111/febs.15548

Proteases and Pseudoproteases in Parasitic Arthropods of Clinical Importance
Fischer, Katja; Fernando, Deepani
https://doi.org/10.1111/febs.15546

Viral pseudoenzymes in infection and immunity
Feng, Pinghui; Wang, Ting-Yu; Zhao, Jun; Savas, Ali; Zhang, Shu
https://doi.org/10.1111/febs.15545