TSPY1 (testis-specific protein Y-linked 1) is a Y chrY-encoded gene with critical roles in male reproduction and potential involvement in cancer development. Structurally, TSPY1 exists in multiple copies organized as tandem repeats in the male-specific region of the Y chrY, with the complete ampliconic structure now characterized in the finished human Y chromosome Y 1. Mechanistically, TSPY1 promotes spermatogonial proliferation by suppressing p53 function through interaction with USP7 and TSPYL5, thereby facilitating G2/M phase transition and reducing cell apoptosis 2. This mechanism is conserved in mice, where TSPYL5 (the autosomal TSPY1 homolog) promotes spermatogonia proliferation via PCNA-mediated DNA replication and p53 degradation 3. Clinically, TSPY1 mutations are associated with male infertility and spermatogenic failure 4, while TSPY1 expression is nearly ubiquitous in individuals with Y chromosome Y and gonadoblastoma, an in situ germ cell neoplasm 5. Beyond reproduction, TSPY1 positively correlates with androgen receptor expression in hepatocellular carcinoma through MAPK/ERK pathway activation 6. Overall, TSPY1 functions as a critical regulator of germ cell proliferation with emerging roles in oncogenic transformation.