ERP29 is an endoplasmic reticulum-resident molecular chaperone encoded on chromosome 12 that plays a critical role in protein folding, trafficking, and secretion within the early secretory pathway 1. Although structurally similar to protein disulfide isomerases with an N-terminal thioredoxin-like domain, ERP29 lacks redox-active function due to absence of catalytic cysteines 2. ERP29 is ubiquitously expressed but upregulated in secretory epithelial cells, neurons, and in response to endoplasmic reticulum stress via the unfolded protein response 1. Beyond protein processing, ERP29 modulates ER homeostasis and cell survival through diverse mechanisms including regulation of ER stress signaling and epithelial-mesenchymal transition pathways 23. In disease contexts, ERP29 demonstrates protective functions: it attenuates nicotine-induced ER stress and choroidal neovascularization in age-related macular degeneration 4, and its downregulation is associated with increased cancer progression and poor prognosis in endometrial and pharyngeal cancers 56. ERP29 expression is regulated by m6A mRNA modifications, linking epigenetic control to its cellular functions 5. These findings position ERP29 as both a central ER quality control protein and an emerging therapeutic target in cancer and neurodegenerative diseases.