ZNF394 is a KRAB-containing zinc finger transcription factor located on chromosome 7.21 that functions as a transcriptional regulator with tissue-specific expression patterns and emerging roles in developmental and disease processes. Structurally, ZNF394 contains an N-terminal leucine-rich region (SCAN domain), a krüppel-associated box (KRAB) domain, and seven C2H2 zinc finger motifs at its C-terminus 1. The protein localizes to the cell nucleus where it exhibits sequence-specific DNA binding activity 1. ZNF394 functions as a transcriptional repressor in mitogen-activated protein kinase signaling pathways, inhibiting the transcriptional activities of c-Jun and AP-1 1. In developmental contexts, ZNF394 plays a critical role in major zygotic genome activation during human early embryogenesis; simultaneous knockdown of ZNF394 and ZIM3 arrests human embryo development prior to the eight-cell stage, while overexpression activates totipotent features in human extended pluripotent stem cells 2. ZNF394 expression is tissue-restricted, being specifically detected in heart, skeletal muscle, and brain 1. Clinically, ZNF394 emerged as a positive prognostic factor in stage I lung squamous cell carcinoma, contributing to a 12-gene prognostic model for risk stratification 3. Additionally, ZNF394 was identified as a key transcription factor in gene regulatory networks associated with total fertilization failure, suggesting involvement in reproductive processes 4.