ZNF521 is a zinc finger transcription cofactor with context-dependent roles as both activator and repressor in multiple developmental and hematopoietic processes. In hematopoiesis, ZNF521 is enriched in hematopoietic stem/progenitor cells where it promotes self-renewal while suppressing differentiation 1. Mechanistically, ZNF521 associates with SMADs in response to BMP2 to activate BMP target genes and functions as a transcriptional repressor through interaction with EBF1, preventing its DNA binding and blocking B-cell lineage specification 2. ZNF521 also cooperates with GLI1/GLI2 transcriptional effectors to enhance Hedgehog pathway signaling, a function dependent on its NuRD complex-binding motif 3. In development, ZNF521 is essential for anterior neural tube closure, where it prevents ectopic closure points while working with ZIC2 and SOX11 in coordinated gene regulatory programs 4. It participates in pelvis morphogenesis through interactions within the SOX9-ZNF521-PTH1R pathway, contributing to human bipedalism evolution 5. Clinically, ZNF521 is upregulated in acute myeloid leukemia (AML) with t(9;11) fusion genes, collaborating with MLL-AF9 to enhance leukemic proliferation, with ZNF521 inhibition inducing cell cycle arrest 1. ZNF521 is dysregulated in multiple cancers including ovarian, pancreatic, hepatocellular, and gastric carcinomas, emerging as a potential diagnostic/prognostic biomarker and therapeutic target 67.