Lin9, a subunit of the DREAM complex, is crucial for regulating cell mitotic processes. It is involved in cell-cycle progression, especially in the transition between different cell-cycle phases such as G(1)/S and G(2)/M [2,3,4]. The DREAM complex, with Lin9 as a core component, plays a significant role in controlling gene expression during the cell cycle, which is essential for normal cell proliferation and development [2,3]. Genetic models, like gene-knockout mouse models, have been instrumental in studying Lin9's functions.

In Lin9-depleted mouse models, loss of Lin9 leads to abolishment of cell proliferation and multiple defects in mitosis and cytokinesis due to down-regulation of a large set of mitotic genes such as Plk1, Aurora A, and Kif20a, indicating its essential role in embryonic development and adult mouse viability [3]. In zebrafish, Lin9-depleted embryonic cells accumulate in mitosis, followed by apoptosis, especially in the developing central nervous system, further validating its role in vertebrate mitosis [4]. In triple-negative breast cancer cells, high Lin9 expression is related to paclitaxel resistance and poor overall survival. Knocking down Lin9 or using BETi (which decreases Lin9 expression) enhances the sensitivity of paclitaxel-resistant cells to paclitaxel, potentially by regulating microtubule-binding protein CCSAP [1]. Also, in lung adenocarcinoma, high Lin9 expression enhances tumorigenesis and predicts poor prognosis [5].

In conclusion, Lin9 is essential for cell mitosis, proliferation, and genome stability. Its dysregulation is associated with various diseases, especially cancer. Studies using KO/CKO mouse models and other genetic manipulation models in different organisms have revealed its role in disease-related processes, providing potential therapeutic targets, such as in breast cancer and lung adenocarcinoma treatment.