ANKZF1 is an endonuclease that functions as a critical component of the ribosome-associated quality control (RQC) pathway, which resolves stalled translation complexes. Its primary function is to cleave polypeptidyl-tRNAs by precisely removing the terminal 3'-CCA nucleotides, thereby releasing ubiquitinated incompletely synthesized polypeptides from 60S ribosomal subunits for proteasomal degradation 1. The cleaved tRNAs are subsequently recycled through a two-step repair process involving ELAC1 phosphatase activity and TRNT1-mediated CCA re-addition 12. Beyond translation quality control, ANKZF1 plays essential roles in mitochondrial proteostasis. It localizes to the cytoplasm and translocates to mitochondria under cellular stress, maintaining mitochondrial integrity and respiration 3. ANKZF1 participates in PINK1-Parkin-mediated mitophagy by physically interacting with Parkin and LC3 via LC3-interacting regions (LIRs), facilitating clearance of stress-damaged mitochondria 4. In glioblastoma, ANKZF1 knockdown promotes intramitochondrial protein aggregation through mitochondrial RQC dysfunction, activating the unfolded protein response and triggering mitochondrial apoptosis 5. Clinically, ANKZF1 dysfunction associates with infantile-onset inflammatory bowel disease through loss-of-function mutations impairing mitochondrial responses to stress 3. Conversely, high ANKZF1 expression correlates with poor survival in colorectal cancer 6. ANKZF1 depletion reduces repeat-associated non-AUG translation in C9ORF72 and FMR1 repeat expansion disorders, suggesting therapeutic potential 7.