ZNF445 is a zinc finger transcription factor serving as a primary regulator of genomic imprinting, essential for maintaining parent-of-origin-specific gene expression patterns 1. The protein contains 14 C2H2 zinc finger motifs, a KRAB domain, and a SCAN domain 2, enabling it to bind imprinting control regions (ICRs) and regulate DNA methylation at multiple differentially methylated regions (DMRs) during early embryonic development 1. In humans, ZNF445 acts as the major imprinting maintenance factor, often working alongside ZFP57 but maintaining critical imprints independently, particularly the MEG3/DLK1:IG-DMR 3. In contrast, murine ZFP57 plays the predominant role, with ZNF445 providing secondary support 1. ZNF445 mutations cause multilocus imprinting disturbance (MLID), characterized by aberrant methylation patterns across multiple DMRs 4. Homozygous truncating ZNF445 variants result in severe hypomethylation at imprinted loci and clinical presentations including Temple syndrome with neurodevelopmental delay 3. ZNF445 is expressed in preimplantation embryos and oocytes 5, suggesting involvement in both imprint establishment and maintenance. Beyond imprinting, ZNF445 can activate AP1 and SRE transcriptional activities through MAPK pathway signaling 2. Clinical significance lies in identifying ZNF445 pathogenic variants in imprinting disorder patients, particularly those with MLID phenotypes affecting growth and developmental outcomes.