Endoplasmic reticulum aminopeptidase 2 (ERAP2) is a proteolytic enzyme involved in adaptive immunity. The ERAP2 gene is highly polymorphic and encodes haplotypes that confer resistance against lethal infectious diseases, but also increase the risk for autoimmune disorders. Identifying how ERAP2 influences susceptibility to these traits requires an understanding of the selective pressures that shaped and maintained allelic variation throughout human evolution. Our review discusses the genetic regulation of haplotypes and diversity in naturally occurring ERAP2 allotypes in the global population. We outline how these ERAP2 haplotypes evolved during human history and highlight the presence of Neanderthal DNA sequences in ERAP2 of modern humans. Recent evidence suggests that human adaptation during the last ~10,000 years and historic pandemics left a significant mark on the ERAP2 gene that determines susceptibility to infectious and inflammatory diseases today.

内质网氨肽酶 2 （ERAP2） 是一种参与适应性免疫的蛋白水解酶。ERAP2 基因具有高度多态性，编码的单倍型赋予对致命传染病的抵抗力，但也会增加自身免疫性疾病的风险。确定 ERAP2 如何影响对这些性状的易感性，需要了解在整个人类进化过程中塑造和维持等位基因变异的选择压力。我们的综述讨论了全球人群中天然存在的 ERAP2 同种异型单倍型和多样性的遗传调控。我们概述了这些 ERAP2 单倍型在人类历史上是如何进化的，并强调了现代人类 ERAP2 中存在尼安德特人 DNA 序列。最近的证据表明，人类在过去 ~10,000 年的适应和历史上的大流行病在 ERAP2 基因上留下了重要的印记，该基因决定了当今对传染病和炎症性疾病的易感性。