Cdyl, also known as chromodomain Y-like, acts as a crotonyl-CoA hydratase. It negatively regulates histone crotonylation (Kcr), an epigenetic modification associated with active transcription [3]. This regulation is linked to multiple cellular pathways such as homologous recombination-mediated DNA repair [1], spermatogenesis [3], and gene expression regulation in processes like sex determination [4]. Genetic models, especially gene knockout (KO) mouse models, are valuable for studying Cdyl's functions.

In Cdyl-deficient mice, several phenotypes were observed. In some Cdyl-deficient mice, XY sex reversal occurred due to derepression of the ovary-promoting gene Wnt4 and down-regulation of the testis-promoting gene Sox9, indicating its role in male gonadal sex determination [4]. In ADPKD mouse models, Cdyl down-regulation was accompanied by increased histone Kcr, and genetic overexpression of Cdyl reduced histone Kcr and slowed cyst growth, suggesting its role in ADPKD progression [2]. In cisplatin-induced AKI mice, overexpression of CDYL aggravated tubular injury and pyroptosis, while treatment with a CDYL inhibitor attenuated kidney dysfunction, showing its potential as a therapeutic target for AKI [5]. In a glioma xenograft mouse model, CDYL knockdown decreased cell mobility in vitro and reduced tumor burden in vivo, with changes in immune pathways and macrophage polarization [6].

In conclusion, Cdyl is crucial for regulating histone crotonylation and is involved in various biological processes and disease conditions. The use of KO and other genetic mouse models has revealed its roles in male gonadal sex determination, ADPKD, AKI, and glioma. Understanding Cdyl's functions provides insights into the mechanisms of these diseases and potential therapeutic strategies.