Xist, short for X inactive-specific transcript, is a long non-coding (lnc)RNA gene. It is the master regulator of X chromosome inactivation (XCI) in mammals, a crucial dosage compensation mechanism between the sex chromosomes of males and females [1,6]. Xist RNA accumulates along the entire length of the chromosome from which it is transcribed, recruiting factors to modify chromatin and silence X-linked genes in cis [1].

In adult human B cells, XIST is continually required to silence a subset of X-linked immune genes like TLR7, through histone deacetylation and without promoter DNA methylation [2]. In naive human pluripotent stem cells (hPSCs), XIST spreads across the X chromosome, dampening X-linked gene expression, and also targets specific autosomal regions to induce repressive chromatin changes and gene expression dampening [3]. XIST has been found to play pathophysiological roles in brain tumors, being involved in processes such as migration, proliferation, angiogenesis, chemoresistance, and apoptosis evasion, especially in gliomas [4]. In NSCLC, XIST is an oncogene, abnormally upregulated, and participates in cell proliferation, invasion, migration, apoptosis, and chemosensitivity [5]. It also functions in diseases like Alzheimer's disease, where aberrations in Xist expression may be significant [7].

In conclusion, Xist is essential for X chromosome inactivation, playing a pivotal role in various biological processes and disease conditions. Studies on Xist, including those using gene-knockout models, have enhanced our understanding of its functions in diseases such as brain tumors, NSCLC, and Alzheimer's disease, providing potential insights for diagnosis, prognosis, and therapeutic strategies.