ZKSCAN3 is a zinc finger transcription factor that functions as a master repressor of autophagy and lysosomal biogenesis in human cells 1. It binds to consensus DNA sequences and transcriptionally represses autophagy-related genes including MAP1LC3B, ULK1, and WIPI2, opposing the autophagy-promoting effects of TFEB 1. ZKSCAN3 regulates autophagy through mTORC1-independent pathways via protein kinase C 2. Beyond autophagy regulation, ZKSCAN3 maintains heterochromatin stability and genomic integrity by interacting with heterochromatin-associated and nuclear lamina proteins, thereby attenuating cellular senescence 3. This epigenetic function is independent of its autophagy-repressing activity 3. In disease contexts, ZKSCAN3 is significantly upregulated across multiple cancer types and correlates with poor prognosis and therapeutic resistance 4. In Parkinson's disease models, ZKSCAN3 overexpression suppresses autophagy-lysosome pathway activation through TFEB inhibition, exacerbating pathology 5. Functionally, ZKSCAN3 exhibits context-dependent plasticity: it promotes cancer progression, invasion, and metastasis while inhibiting apoptosis 4, yet paradoxically suppresses tumor initiation through genomic stability maintenance 6. Its subcellular localization and activity are dynamically regulated by post-translational modifications including phosphorylation and ubiquitination 6. ZKSCAN3 represents both a prognostic biomarker and promising therapeutic target in oncology and neurodegenerative diseases.