{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T21:21:47Z","timestamp":1792531307267,"version":"4.5.0"},"reference-count":105,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,2,20]],"date-time":"2024-02-20T00:00:00Z","timestamp":1708387200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Aminopeptidases are a group of enzymatic proteins crucial for protein digestion, catalyzing the cleavage of amino acids at the N-terminus of peptides. Among them are ERAP1 (coding for endoplasmic reticulum aminopeptidase 1), ERAP2 (coding for endoplasmic reticulum aminopeptidase 2), and LNPEP (coding for leucyl and cystinyl aminopeptidase). These genes encoding these enzymes are contiguous and located on the same chromosome (5q21); they share structural homology and functions and are associated with immune-mediated diseases. These aminopeptidases play a key role in immune pathology by cleaving peptides to optimal sizes for binding to the major histocompatibility complex (MHC) and contribute to cellular homeostasis. By their ability to remove the extracellular region of interleukin 2 and 6 receptors (IL2, IL6) and the tumor necrosis factor receptor (TNF), ERAP1 and ERAP2 are involved in regulating the innate immune response and, finally, in blood pressure control and angiogenesis. The combination of specific genetic variations in these genes has been linked to various conditions, including autoimmune and autoinflammatory diseases and cancer, as well as hematological and dermatological disorders. This literature review aims to primarily explore the impact of ERAP1 polymorphisms on its enzymatic activity and function. Through a systematic examination of the available literature, this review seeks to provide valuable insights into the role of ERAP1 in the pathogenesis of various diseases and its potential implications for targeted therapeutic interventions. Through an exploration of the complex interplay between ERAP1 and various disease states, this review contributes to the synthesis of current biomedical research findings and their implications for personalized medicine.<\/jats:p>","DOI":"10.3390\/cimb46030107","type":"journal-article","created":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T08:43:48Z","timestamp":1708505028000},"page":"1651-1667","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["The Role of Aminopeptidase ERAP1 in Human Pathology\u2014A Review"],"prefix":"10.3390","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4401-7934","authenticated-orcid":false,"given":"Laura","family":"\u021aiburc\u0103","sequence":"first","affiliation":[{"name":"Faculty of Medicine and Pharmacy, University of Oradea, Universit\u0103\u021bii Street 1, 410087 Oradea, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4021-4989","authenticated-orcid":false,"given":"Dana Carmen","family":"Zaha","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Pharmacy, University of Oradea, Universit\u0103\u021bii Street 1, 410087 Oradea, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Claudia","family":"Jurca","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Pharmacy, University of Oradea, Universit\u0103\u021bii Street 1, 410087 Oradea, Romania"},{"name":"Regional Center of Medical Genetics Bihor, County Emergency Clinical Hospital, Bihor, 65\u201367, Gheorghe Doja Street, 410169 Oradea, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3901-615X","authenticated-orcid":false,"given":"Emilia","family":"Severin","sequence":"additional","affiliation":[{"name":"Department of Genetics, Carol Davila University of Medicine and Pharmacy, Dionisie Lupu 37 Street, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurora","family":"Jurca","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Pharmacy, University of Oradea, Universit\u0103\u021bii Street 1, 410087 Oradea, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandru Daniel","family":"Jurca","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Pharmacy, University of Oradea, Universit\u0103\u021bii Street 1, 410087 Oradea, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1016\/j.biochi.2010.04.026","article-title":"Metallo-Aminopeptidase Inhibitors","volume":"92","author":"Mucha","year":"2010","journal-title":"Biochimie"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1038\/s41413-019-0057-8","article-title":"Ankylosing Spondylitis: Etiology, Pathogenesis, and Treatments","volume":"7","author":"Zhu","year":"2019","journal-title":"Bone Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1576","DOI":"10.3389\/fimmu.2020.01576","article-title":"The Multifaceted Nature of Aminopeptidases ERAP1, ERAP2, and LNPEP: From Evolution to Disease","volume":"11","author":"Paladini","year":"2020","journal-title":"Front. 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