ZNF397 is a SCAN domain-containing C2H2 zinc finger protein that functions as a transcriptional regulator with context-dependent roles 1. The protein exists in multiple isoforms generated through alternative splicing; the full-length isoform acts as a transcriptional activator, while the N-terminal SCAN domain-only isoforms function as transcriptional repressors 1. ZNF397 localizes to the nucleus and serves as a coactivator of androgen receptor (AR) signaling, essential for maintaining AR-driven luminal lineage transcription in prostate cells 2. Additionally, ZNF397 localizes to centromeres during interphase and early prophase, functioning as an interphase-specific centromere protein, though its centromere function remains incompletely understood 3. In prostate cancer, ZNF397 deficiency promotes lineage plasticity and therapy resistance by enabling TET2-driven epigenetic reprogramming, allowing cancer cells to escape AR-targeted treatments 2. ZNF397 is expressed broadly across tissues with varying transcript isoforms 1, and genetic variants near ZNF397 have been associated with plasma amyloid-beta levels in Alzheimer's disease endophenotype studies 4. ZNF397 is non-essential in mice, suggesting redundant functions in normal development 3.