NSUN7 is an m5C (5-methylcytosine) RNA methyltransferase belonging to the NOP2/Sun domain family that catalyzes site-specific methylation of RNA substrates. 1 The protein localizes to the cytoplasm and sperm flagellum, where it regulates gene expression at the posttranscriptional level by destabilizing specific RNA transcripts in elongated spermatids. 1 Mechanistically, NSUN7 catalyzes m5C modifications on target RNAs including NLRP3, CCDC9B, and circNTRK2, which affects mRNA stability and downstream signaling. 234 The methylation regulates reader protein binding and RNA accessibility, influencing transcript availability for translation and protein expression. NSUN7 dysfunction is associated with multiple disease states. Mutations cause male infertility through mispositioning of sperm flagellar structures and motility defects. 1 Epigenetic silencing via promoter hypermethylation occurs in liver cancer and correlates with poor survival and therapeutic vulnerabilities including bromodomain inhibitor sensitivity. 3 NSUN7 upregulation promotes progression in cervical cancer via ErbB pathway activation and in glioblastoma through circRNA-mediated stemness. 54 Conversely, reduced NSUN7 expression contributes to polycystic ovary syndrome pathogenesis through NLRP3-mediated pyroptosis. 2 NSUN7 also emerges as a sepsis biomarker with diagnostic potential. 6