L1TD1, also known as FLJ10884 or ECAT11, is a cytoplasmic RNA-binding protein. It is specifically expressed in pluripotent stem cells and is essential for maintaining stemness in human cells [2,3,4,6]. L1TD1 is the only known protein-coding gene domesticated from a LINE-1 (L1) retroelement [2]. It has roles in RNA splicing, translation, protein traffic, and degradation, and is part of the pluripotency interactome network of OCT4, SOX2, and NANOG, bridging nuclear and cytoplasmic regulation [3].

In colon cancer, increased L1TD1 expression is a positive prognostic marker associated with longer disease-free survival, contrasting with its role in medulloblastoma where high expression is linked to poor prognosis [1,7]. In medulloblastoma, L1TD1 is required for cell viability, neurosphere formation, and chemoresistance. Depletion of L1TD1 reduces cell viability, inhibits cell proliferation, and induces apoptosis, while also sensitizing cells to chemotherapeutic agents [7]. In non-small cell lung cancers, L1TD1 is tumor-specifically methylated, and DNA methylation is involved in its transcriptional regulation. Overexpression of L1TD1 in NSCLC cells shows tumor-cell growth suppressing properties [5].

In conclusion, L1TD1 is crucial for maintaining stemness in human pluripotent stem cells. Its role varies in different disease contexts. In colon cancer, it serves as a positive prognostic marker, while in medulloblastoma, it is associated with a more aggressive tumor phenotype. In non-small cell lung cancers, its methylation-related transcriptional regulation impacts tumor-cell growth. Studies on L1TD1 contribute to understanding disease mechanisms and may offer potential therapeutic targets.