DNAJB11 is an endoplasmic reticulum (ER) co-chaperone that functions as a critical regulator of protein quality control and cyst formation in polycystic kidney disease. As a co-chaperone for HSPA5, DNAJB11 binds directly to unfolded proteins destined for ER-associated degradation (ERAD) and nascent polypeptide chains, stimulating HSPA5 ATPase activity to facilitate proper protein folding, trafficking, or degradation 12. DNAJB11 is essential for maturation and correct trafficking of Polycystin-1 (PC1), the major ADPKD protein 3. Functionally, DNAJB11 works within a multiprotein complex alongside SDF2 and SDF2L1 co-factors, which are interdependent for PC1 processing 4. Clinically, DNAJB11 mutations cause autosomal dominant polycystic kidney disease (ADPKD) as a minor gene locus, accounting for atypical disease forms with disease severity comparable to PKD2 mutations 5. Biallelic Dnajb11 loss causes cystic kidney disease with cysts predominantly originating from proximal tubules, and impaired PC1 cleavage represents a key pathogenic mechanism 6. Unlike classical PKD1-driven disease, DNAJB11-related cysts form in utero, with timing of inactivation strongly influencing severity 6. Genetic studies demonstrate that DNAJB11 variants, alongside other ER protein synthesis pathway genes, reduce functional polycystin dosage below critical thresholds, triggering cyst formation 7.