TMSB4Y (thymosin beta 4 Y-linked) is a Y chrY-encoded gene that functions as a tumor suppressor with roles in cytoskeletal organization and cell cycle regulation. The protein directly interacts with β-actin and sequesters actin monomers, affecting cytoskeletal dynamics 1. In male esophageal squamous cell carcinoma, TMSB4Y inhibits proliferation, invasion, and metastasis by disrupting PAICS octamer formation, which impairs purine synthesis and AMPK signaling, ultimately suppressing sphingomyelin metabolism 2. TMSB4Y expression in breast epithelial cells results in aberrant cellular morphology, reduced proliferation, and decreased metaphase cell fraction 1. The gene shows differential expression patterns across various cancers, including prostate cancer and male breast cancer, where clonal loss occurs in ~16% of cases 31. TMSB4Y has been identified as a biomarker in multiple disease contexts, including ankylosing spondylitis, Alzheimer's disease, major depressive disorder, lymphoma radiotherapy resistance, and proliferative diabetic retinopathy 4567. Additionally, TMSB4Y encodes a minor histocompatibility antigen recognized by CD8+ T cells in transplant settings, highlighting its immunological significance 8.