The impact of X chromosome inactivation on human health

X chromosome inactivation (XCI) is a crucial genetic regulatory mechanism in female cells, wherein one of the two X chromosomes is randomly silenced to balance gene expression between sexes. Despite the overall silencing, approximately 15%-30% of human genes escape XCI, leading to their biallelic expression in females. Many studies have highlighted the phenomenon of XCI skewing, where the inactivation is preferentially biased towards one X chromosome. XCI escape and XCI skewing are significantly associated with various health issues, including autoimmune disorders, neurodevelopmental disorders (NDDS), cardiovascular diseases (CVD) and cancer, etc. This review aims to provide a comprehensive overview of the mechanisms underlying XCI, its roles across different genders and disease states, and to explore the intricate relationship between XCI and human health. By emphasizing the significance of understanding XCI, this article seeks to shed light on potential therapeutic targets and avenues for further research in the field.