DNAJB9 is an endoplasmic reticulum (ER)-luminal co-chaperone of heat shock protein 70 (HSPA5/BiP) that functions as a key regulator of cellular protein quality control and stress responses. Mechanistically, DNAJB9 represses the IRE1-mediated unfolded protein response (UPR) by recruiting BiP to prevent dimerization and activation of the ER stress sensor ERN1/IRE1 1. Additionally, DNAJB9 participates in endoplasmic reticulum-associated degradation (ERAD), facilitating clearance of misfolded proteins including the cystic fibrosis transmembrane conductance regulator (CFTR); DNAJB9 knockdown increases surface expression of both wild-type and ΔF508-CFTR 2. Beyond ER homeostasis, DNAJB9 inhibits p53-dependent oncogene-induced senescence, promoting neoplastic transformation through direct p53 interaction 3. Clinically, DNAJB9 has emerged as a highly specific and sensitive biomarker (98% sensitivity, 99% specificity) for diagnosing fibrillary glomerulonephritis, a rare renal disease characterized by 12-24 nm fibrils in glomeruli 45. DNAJB9 expression is upregulated in response to various cellular stressors, including cadmium exposure and single-walled carbon nanotubes 67. Furthermore, elevated DNAJB9 levels associate with accelerated aging phenotypes and increased risk of age-related diseases in socially disadvantaged populations 8.