ZNF354C is a transcriptional repressor that plays crucial roles in vascular biology and cellular differentiation. The protein functions as a potent transcriptional repressor through its active KRAB domain, which mediates gene suppression by interacting with dsDNA, TRIM28, and histones 1. ZNF354C localizes to both nucleus and cytoplasm and specifically inhibits endothelial angiogenic sprouting by binding to endothelial-relevant target gene promoters 1. The protein's repressive activity requires specific amino acids (DV and MLE) within its KRAB domain 1. In disease contexts, ZNF354C demonstrates protective functions in lung ischemia-reperfusion injury by reducing TFPI promoter methylation and upregulating TFPI expression 2. The protein is also involved in cancer biology, where disruption of the HDAC6-TRIM28-ZNF354C corepressor complex by LINC00624 promotes hepatocellular carcinoma progression 3. Additionally, ZNF354C has been identified as a hub gene associated with mortality in tuberculous meningitis and osteosarcoma 45. Its regulatory network involvement spans cardiovascular disease, where it facilitates MMP2 gene expression in dilated cardiomyopathy 6.