ZNF658 is a zinc-responsive transcriptional repressor that coordinates cellular zinc homeostasis with ribosome biogenesis. The protein contains a KRAB domain and 21 zinc fingers 1, binding to zinc transcriptional regulatory elements (ZTREs) with a consensus sequence of 5'-C[AC]C[TAG]CC[TC]-N(0-50)-[GA]G[ATC]G[TG]G-3' found in gene promoters 2. Upon zinc elevation, ZNF658 represses expression of zinc transporter genes (SLC30A5, SLC30A10) and other zinc homeostasis regulators 1. Critically, ZNF658 regulates ribosomal RNA precursor transcription and ribosomal protein expression by binding ZTREs clustered within the 45S rRNA precursor, functionally linking zinc availability to ribosome production—the cell's most zinc-demanding process 1. The protein exhibits context-dependent binding affinity, potentially suppressing both zinc-compensatory and transcriptional activation genes depending on cellular zinc status 2. Clinically, genomic deletions of ZNF658 are associated with increased risk of arsenic-induced skin lesions in exposed populations, with gender-specific effects, suggesting ZNF658 participates in arsenic toxicity resistance 3. This dual functionality as a zinc-responsive regulator and ribosome biogenesis coordinator positions ZNF658 as a fundamental mediator of cellular zinc-dependent physiology.