RNASE10 is a secreted epididymal protein essential for male reproductive function, despite being catalytically inactive as a ribonuclease. In the epididymis, RNASE10 is required for post-testicular sperm maturation and male fertility 1. The protein plays a critical role in sperm-egg interaction, likely facilitating sperm adhesion to the zona pellucida 1. RNASE10 expression is downstream of ROS1 signaling in the epididymis; when ROS1 is inhibited, RNASE10 levels decrease, leading to impaired sperm maturation, reduced zona pellucida binding capacity, and compromised sperm motility 1. These fertility defects are reversible upon cessation of ROS1 inhibition, suggesting RNASE10's role is functional rather than structural. Beyond reproduction, RNASE10 has emerged as a prognostic biomarker in head and neck squamous cell carcinoma (HNSCC). It was identified as an independent prognostic factor in HNSCC 2 and incorporated into a nine-gene RNA-binding protein prognostic model predicting overall survival 3. The differential expression of RNASE10 in HNSCC tissues indicates potential involvement in cancer pathogenesis, though the mechanistic connection between its reproductive and oncological roles remains unclear.