ZNF219 is a nuclear zinc finger transcription factor containing nine C2H2 zinc finger domains that recognizes the core DNA sequence motif 5'-CCCCC-3' 1. The protein functions as both a transcriptional repressor and activator depending on promoter context. ZNF219 represses HMGN1 expression 1 and prototype foamy virus replication through 5'LTR targeting 2. Conversely, ZNF219 activates chondrogenic gene expression by forming a transcriptional complex with SOX9 to enhance COL2A1, aggrecan, and COL11A2 expression during chondrocyte differentiation 3. Beyond skeletal development, ZNF219 is phosphorylated by CDKL5 in neurons and associates with the NuRD chr14 remodeling complex, regulating neuronal activity-dependent genes 4. ZNF219 also regulates SNCA expression in primary cortical neurons and represses neural differentiation in radial glia 5. Clinically, ZNF219 loss enhances anti-tumor immunity in aged T cells by inducing cytotoxic gene reprogramming, and high ZNF219 expression correlates with poorer survival following immune checkpoint blockade 6. Additionally, ZNF219 protects lens epithelial cells against oxidative stress via AKT/GSK3β pathway activation, suggesting roles in cataract pathogenesis 7. ZNF219 exhibits developmentally regulated transcript sizes and ubiquitous tissue expression 8.