ZNF598 is an E3 ubiquitin ligase that serves as a critical quality control sensor for ribosomal dysfunction. Its primary function involves detecting collided ribosomes that form when trailing ribosomes encounter stalled leading ribosomes during translation 1. ZNF598 specifically recognizes the collided di-ribosome structure and ubiquitinates ribosomal proteins RPS2, RPS3, RPS10, and RPS20 on the 40S subunit 12. This ubiquitination initiates ribosome-associated quality control (RQC) pathways that resolve aberrant translation complexes and promote degradation of faulty mRNAs and nascent polypeptides 3. ZNF598 activity is regulated through K63-linked ubiquitination by CNOT4 and is upregulated during mitochondrial stress 4. The protein plays distinct roles in different contexts: it negatively regulates interferon-stimulated gene expression but is required for poxvirus protein synthesis by facilitating translation of mRNAs with unusual 5' poly(A) leaders 5. ZNF598 can also interact with the DNA sensor cGAS, linking translation stress to innate immune activation 6. Single-molecule studies reveal that ZNF598 is a rate-limiting factor in RQC and can engage multiple sites on aberrant mRNAs 7.