ZNF354A (zinc finger protein 354A) is a KRAB-zinc finger transcription factor that functions as an epigenetic repressor with significant roles in cellular defense mechanisms and development. The protein contains a Krüppel-associated box (KRAB) domain and belongs to the C2H2 class of zinc finger proteins 1. ZNF354A serves as a key component of the Lipid Oxygen Radical Defense (LORD) pathway, where it forms a repressive complex with KAP1/TRIM28, SETDB1, and ATF2 to epigenetically silence protective genes under normal conditions 2. Upon lipid peroxide accumulation, stress-induced phosphorylation leads to complex disassembly and ZNF354A release from DNA, activating antioxidant gene networks including NRF2 targets 2. The gene shows tissue-specific expression patterns, being expressed in kidney, inner ear structures, and various other tissues 1. ZNF354A is upregulated in testicular germ cell tumors during the precursor intratubular germ cell neoplasia stage 3 and shows altered expression in COVID-19 recovery patients 4. Additionally, genetic variants in ZNF354A are associated with breast cancer risk 5. The gene maps to chromosome 5.3, a region frequently altered in renal cell carcinomas 6.