Kdm5d, also known as lysine-specific demethylase 5D, is a histone demethylase. It plays a role in chromatin-related processes by mediating demethylation, which can influence gene expression. It is associated with pathways related to cell cycle regulation, cell adhesion, and kinase-signaling cascades, and is of great biological importance in understanding cancer development and other biological processes. Genetic models, such as KO/CKO mouse models, are valuable for studying its functions.

In a murine CRC model (iKAP), deletion of Kdm5d in cancer cells increased tight junction integrity, decreased cell invasiveness, and enhanced cancer cell killing by CD8+ T cells, suggesting that KRAS*-STAT4-mediated upregulation of Kdm5d contributes to sex differences in KRAS* CRC by disrupting cancer cell adhesion and tumour immunity [1]. In NSCLC, Kdm5d interacts with p38α, mediating demethylation at K165 and inhibiting p38α phosphorylation, thus suppressing tumour progression [2]. In HNSCC, Kdm5d knockdown reduced the tolerance of persister cells to platinum agents and caused cell cycle deregulation, indicating its role in the development of persister cells [3].

In conclusion, Kdm5d is a crucial histone demethylase involved in multiple biological processes. Through model-based research, especially KO/CKO mouse models, its role in cancer-related processes such as metastasis, tumour cell proliferation, and drug tolerance has been revealed. These findings contribute to understanding the molecular mechanisms of cancer and potentially offer new therapeutic strategies for related diseases.