Nsun5, also known as NOP2/Sun RNA methyltransferase 5, is an enzyme in the 5-methylcytosine (m5C) writer family that modifies rRNA and mRNA. It is involved in multiple biological processes such as regulating ferroptosis, immune evasion, lipid metabolism, maternal-to-zygotic transition, and early embryonic development. These processes are associated with various disease conditions including cancer, highlighting its biological importance. Genetic models like KO mouse models are valuable for studying its functions [1,2,3,4,8].

In BMSCs, Nsun5 knockdown enhances erastin-induced ferroptosis, while its overexpression inhibits it, suggesting the Nsun5-FTH1/FTL pathway mediates ferroptosis [1]. In glioma, Nsun5 down-regulates β-catenin and affects chromatin-associated RNA modification, which may be related to immune evasion [2]. In PCa cells, CDK13 promotes lipid deposition by phosphorylating Nsun5, which then modifies ACC1 mRNA [3]. In mouse ovaries, Nsun5KO obstructs follicular development and ovarian function, indicating its importance in the maternal-to-zygotic transition [4]. In HCC, Nsun5 is upregulated, promoting tumor proliferation and migration [5,6]. In GC cells, the Nsun5-FTH1 axis inhibits ferroptosis and promotes cell growth [7]. In mouse preimplantation embryos, Nsun5 knockdown leads to developmental impairments, disrupted cell differentiation, and upregulation of Hippo signaling-related genes [8].

In conclusion, Nsun5 is crucial for various biological processes, and its dysregulation is associated with multiple diseases, especially different types of cancers. KO mouse models have significantly contributed to understanding its role in these processes and diseases, helping to potentially identify new therapeutic targets.