Check the content of the review Id2, short for Inhibitor of DNA binding protein 2, is a helix-loop-helix negative transcription regulatory factor. It plays diverse roles in multiple biological processes, involving in cell differentiation, immune responses, and tissue-specific functions. It is associated with pathways such as those related to cell cycle regulation, epigenetic modification, and signal transduction, which are crucial for normal development and disease-related processes [2,4,5]. Genetic models, especially knockout (KO) mouse models, are valuable for studying its functions.

In CD8+ T-cell exhaustion, genetic deletion of Id2 dampens CD8+ T-cell-mediated immune responses, suppresses PD-1 blockade, and increases tumor susceptibility. Id2 epigenetically regulates the generation of Slamf6+ progenitor exhausted (Texprog) cells and their conversion to Tim-3+ terminally exhausted (Texterm) cells by disrupting the assembly of the Tcf3-LSD1 complex [1]. In the small intestine, loss of Id2 in mice leads to changes in the number of enteroendocrine cells and tuft cells, indicating its role in cell fate decisions along the anterior-posterior and crypt-villi axes [3]. In hematopoietic stem cells (HSCs), ablation of Id2 in adult mice promotes HSC activation, differentiation, and exhaustion over time, with Id2Δ/Δ HSCs showing increased cycling and DNA damage [6].

In conclusion, Id2 has essential biological functions in cell differentiation, immune regulation, and stem cell quiescence. Studies using KO mouse models have revealed its significance in tumor-immune evasion, gut cell fate determination, and HSC maintenance. These findings contribute to understanding disease mechanisms in areas such as cancer and hematological disorders, providing potential targets for therapeutic intervention.