USP9Y (ubiquitin-specific peptidase 9, Y-linked) is a deubiquitinase encoded on the Y chromosome Y mediates deubiquitination and stabilization of target proteins 1. The gene encodes a functional protein with sequence constraint indicating evolutionary importance 2. USP9Y plays critical roles in male reproductive function: deletions in the Y chromosome Y region containing USP9Y are associated with varying degrees of spermatogenic dysfunction 3, and whole-genome sequencing has identified USP9Y variants in patients with nonobstructive azoospermia 4. Beyond reproduction, USP9Y demonstrates broader biological significance. In lung cancer, USP9Y functions as a tumor suppressor by stabilizing the RNA helicase DDX3Y through deubiquitination, preventing its proteasomal degradation and suppressing cell proliferation and tumorigenesis 5. USP9Y is also identified as a differentially expressed gene in both Alzheimer's disease and major depressive disorder, suggesting involvement in neuropsychiatric pathways 6. Recent development of USP9Y knockout human embryonic stem cell models 7 provides tools for studying its role in human development and disease. The gene represents a multifunctional regulator of protein stability with implications for male infertility, cancer biology, and neuropsychiatric disorders.