ZNF503 is a zinc finger transcriptional repressor that negatively regulates cell proliferation and gene expression 1. It functions by repressing GATA3, a master regulator of mammary epithelial differentiation, through recruitment to the GATA3 promoter in association with ZBTB32 1. This repressive activity promotes epithelial cell proliferation and aggressive cancer development. In triple-negative breast cancer, the ZNF503/GATA3 ratio serves as a prognostic biomarker, with elevated ZNF503 correlating with poor outcomes 2. ZNF503 is targeted by miR-340-5p, which suppresses non-small cell lung cancer cell growth and metastasis 3. Conversely, the antisense lncRNA ZNF503-AS1 promotes retinal pigment epithelium differentiation by downregulating ZNF503 expression, preventing dedifferentiation in age-related macular degeneration 4. In bladder cancer, decreased ZNF503-AS1 expression correlates with tumor progression; ZNF503-AS1 restores calcium homeostasis through GATA6-mediated SLC8A1 upregulation, suppressing cancer cell proliferation 5. The related lncRNA ZNF503-AS2 is upregulated in glioblastoma and associates with immunosuppression; its knockdown reduces glioma cell proliferation and invasion 6. Overall, ZNF503 functions as an oncogenic repressor of differentiation factors, while its antisense lncRNAs act as tumor suppressors in multiple cancer types.