DNLZ (DNL-type zinc finger) is a mitochondrial co-chaperone protein that functions as a critical regulator of HSPA9/mortalin, the human mitochondrial Hsp70 chaperone. The zinc-binding subdomain (ZBS) of DNLZ is essential for stable complex formation with HSPA9's ATPase domain and for stimulating its catalytic activity 1. A conserved histidine residue within DNLZ is particularly critical for HSPA9 ATPase stimulation 2. DNLZ prevents HSPA9 self-aggregation, maintaining the chaperone in a soluble and functional state to preserve mitochondrial proteostasis 3. Beyond its canonical mitochondrial role, DNLZ interacts with negatively charged lipid bilayers and can be incorporated into cellular membranes in a dose-dependent manner, suggesting extra-mitochondrial functions 4. DNLZ can block formation of HSPA9 supramolecular assemblies under thermal stress and remodel preformed aggregates into smaller forms 5. Clinically, DNLZ variants have been identified in genome-wide association studies as a candidate gene in common pathways for both Type 1 and Type 2 diabetes, where it participates in islet eQTL networks 6. DNLZ phosphopeptides show elevated frequency in sepsis plasma proteomes, suggesting potential involvement in inflammatory disease states 7.