RUNX1是一种转录因子，是胚胎发育和产后巨核细胞生成过程中造血谱系特异性的主要调节因子。RUNX1的突变和重排是造血系统恶性肿瘤的主要驱动因素。在人类中，该基因位于第21号染色体的“唐氏综合症关键区”，其中三倍体化对于大部分唐氏综合症特征的表现是必要且充分的。唐氏综合症患者易患白血病。因此，RUNX1过表达最初被提出作为唐氏综合症相关白血病发生的关键因素。虽然越来越多的报告显示RUNX1在其他组织和器官中对神经组织、肌肉、心脏、骨骼、卵巢或内皮等的发育或稳态具有重要影响，但对于唐氏综合症背景下RUNX1基因剂量变化对这些组织的后果了解得更少。在本综述中，我们总结了有关RUNX1在血液/白血病之外的活动的当前知识，同时首次提出了与特定的唐氏综合症并发症的关系。我们简明扼要地回顾了RUNX1在不同组织中的新兴作用，超越了造血背景，提供了一些经过充分支持的假设，将为更好地理解RUNX1介导的健康与疾病中的转录调控打开新的研究方向，为与唐氏综合症相关的疾病提供新的潜在诊断和治疗策略。© 2023. BioMed Central有限公司，施普林格自然出版集团的一部分。

RUNX1 is a transcription factor and a master regulator for the specification of the hematopoietic lineage during embryogenesis and postnatal megakaryopoiesis. Mutations and rearrangements on RUNX1 are key drivers of hematological malignancies. In humans, this gene is localized to the 'Down syndrome critical region' of chromosome 21, triplication of which is necessary and sufficient for most phenotypes that characterize Trisomy 21.Individuals with Down syndrome show a higher predisposition to leukemias. Hence, RUNX1 overexpression was initially proposed as a critical player on Down syndrome-associated leukemogenesis. Less is known about the functions of RUNX1 in other tissues and organs, although growing reports show important implications in development or homeostasis of neural tissues, muscle, heart, bone, ovary, or the endothelium, among others. Even less is understood about the consequences on these tissues of RUNX1 gene dosage alterations in the context of Down syndrome. In this review, we summarize the current knowledge on RUNX1 activities outside blood/leukemia, while suggesting for the first time their potential relation to specific Trisomy 21 co-occurring conditions.Our concise review on the emerging RUNX1 roles in different tissues outside the hematopoietic context provides a number of well-funded hypotheses that will open new research avenues toward a better understanding of RUNX1-mediated transcription in health and disease, contributing to novel potential diagnostic and therapeutic strategies for Down syndrome-associated conditions.© 2023. BioMed Central Ltd., part of Springer Nature.