SERP1 (stress-associated endoplasmic reticulum protein 1) is an ER-resident protein that functions as a Sec61-associated polypeptide facilitating protein translocation and protecting unfolded proteins during ER stress 1. Its primary role involves stabilizing target proteins during translocation into the ER lumen and facilitating their N-linked glycosylation 2. SERP1 regulates the glycosylation and function of specific receptors, including GLP-1R, and can rescue protein function after tunicamycin-induced ER stress 2. Beyond ER proteostasis, SERP1 acts as an APP-biased γ-secretase regulator under metabolic stress conditions, enhancing amyloid-beta generation in cells experiencing ER stress such as diabetes 3. Clinically, SERP1 dysregulation is associated with multiple pathologies: low SERP1 expression correlates with poor prognosis and enhanced immune infiltration in skin cutaneous melanoma 4, while miR-1-3p-mediated SERP1 downregulation contributes to sepsis-induced acute lung injury by promoting endothelial cell dysfunction 5. Conversely, SERP1 overexpression mitigates acute hepatic injury via GSK3β/β-catenin pathway regulation 6 and promotes wound healing through Wnt/β-catenin signaling 7. SERP1 deficiency in mice causes growth retardation, impaired glucose tolerance, and pancreatic dysfunction 1, establishing SERP1 as a critical mediator linking ER stress responses to disease pathogenesis.