ZNF418 is a KRAB/C2H2 zinc finger transcription repressor 1 that regulates cardiac homeostasis and protein degradation pathways. As a transcriptional repressor, ZNF418 suppresses MAPK and AP-1/c-Jun signaling 1, mechanisms critical for controlling cardiac hypertrophy. ZNF418 negatively regulates the ubiquitin-proteasome system while positively regulating autophagy-lysosomal pathway activity, coordinating protein quality control through transcriptional regulation of autophagy activators like DAPK2 and FYCO1 2. In cardiac disease, ZNF418 is significantly downregulated in dilated and hypertrophic cardiomyopathy. ZNF418 overexpression protects against aortic banding and angiotensin II-induced cardiac hypertrophy and fibrosis by suppressing c-Jun phosphorylation 3. In cancer contexts, ZNF418 functions as a tumor suppressor—it is downregulated in hepatocellular carcinoma, gastric cancer, and head/neck squamous cell carcinoma, with reduced expression correlating with advanced disease stage and worse survival 456. miR-1204 promotes hepatocellular carcinoma progression by directly targeting ZNF418 and activating MAPK/c-Jun signaling 4. Clinically, ZNF418 methylation status serves as a biomarker for esophageal and laryngeal squamous cell carcinoma diagnosis and prognosis 78.