Early studies have shown that erythrocytes have caspase-3 and caspase-8 and are capable of dying through an apoptotic-like cell death triggered by Ca2+ ionophores. This cell death is associated with apoptosis-like morphological signs, including cell shrinkage, membrane blebbing, and phosphatidylserine externalization. To emphasize that mature erythrocytes don't have the apoptotic mitochondrial machinery and distinguish this unique cell death modality from apoptosis, it was named "eryptosis". Over recent decades, our knowledge of eryptosis has been significantly expanded, providing more insights into the uniqueness of cell death pathways in erythrocytes. In this review, we aim to summarize our current understanding of eryptosis, formulate the nomenclature and guidelines to interpret results of eryptosis studies, provide a synopsis of morphological and biochemical features of eryptosis, and highlight the role of eryptosis in health and disease, including its druggability.

1st Department of Internal Medicine Hematology General University Hospital and 1st Faculty of Medicine Charles University Prague Czech Republic

BIOCEV 1st Faculty of Medicine Charles University Vestec Czech Republic

Chair of Medical and Molecular Genetics Research Department of Clinical Laboratory Sciences College of Applied Medical Sciences King Saud University Riyadh Saudi Arabia

Department of Biochemistry and Systems Biology Institute of Systems Molecular and Integrative Biology Faculty of Health and Life Sciences University of Liverpool Liverpool UK

Department of Biochemistry University of Agriculture Faisalabad Pakistan

Department of Biological Chemical and Pharmaceutical Sciences and Technologies University of Palermo Palermo Italy

Department of Biophysics of Environmental Pollution Faculty of Biology and Environmental Protection University of Lodz Lodz Poland

Department of Clinical Laboratory Sciences College of Applied Medical Sciences King Saud University Riyadh Saudi Arabia

Department of Cryobiochemistry Institute for Problems of Cryobiology and Cryomedicine of the National Academy of Sciences of Ukraine Kharkiv Ukraine

Department of Nephrology Dialysis and Transplant St Bortolo Hospital Vicenza Italy

Department of Physiological Sciences Faculty of Science Stellenbosch University Stellenbosch South Africa

Department of Physiology University of Hohenheim Stuttgart Germany

Department of Veterinary and Animal Sciences University of Rajshahi 6205 Rajshahi Bangladesh

Institute of Physiology 1 Eberhard Karls University Tübingen Tübingen Germany

IRRIV International Renal Research Institute Vicenza Vicenza Italy

Medicine and Nutrition Faculty Universidad Juárez del Estado de Durango Durango Dgo México

Nutrition and Food Science Area Faculty of Pharmacy and Food Sciences University of Valencia Burjassot Spain

Research Institute of Experimental and Clinical Medicine Kharkiv National Medical University Kharkiv Ukraine

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