Asf1a, short for anti-silencing function 1a, is a histone H3-H4 chaperone isoform. It is involved in chromatin assembling, transcription regulation, and various chromatin-mediated cellular processes [3,5]. It participates in pathways related to cell differentiation, DNA repair, and immunity, holding great biological importance. Genetic models, such as KO/CKO mouse models, are valuable for studying its functions.

In atherosclerosis, endothelium-specific Asf1a deficiency in Apoe KO Asf1a ECKO mice inhibits endothelial-to-mesenchymal transition (EndMT) and alleviates atherosclerosis development. This indicates that Asf1a, as a cofactor of P300, promotes atherosclerosis by regulating EndMT through histone H3 lysine 18 lactylation [1]. In Kras-mutant lung adenocarcinoma, loss of Asf1a in tumor cells in a mouse model sensitizes tumors to anti-PD-1 treatment, suggesting its potential as an immunotherapeutic target [2]. In cancer cells, ASF1a knockdown leads to growth arrest and senescence in wild-type p53-carrying cells, revealing its importance in cancer cell proliferation [3]. In chronic myeloid leukemia, ASF1A is up-regulated in blast crisis patients, and its inhibition may be a therapeutic approach as it activates Notch signaling to mediate differentiation arrest [4].

In conclusion, Asf1a is crucial in multiple biological processes. Model-based research, especially KO/CKO mouse models, has revealed its roles in diseases like atherosclerosis, lung adenocarcinoma, various cancers, and chronic myeloid leukemia. These findings provide potential therapeutic targets and biomarkers for these disease areas.