RESP18 (regulated endocrine-specific protein 18) is a novel 18-kDa endoplasmic reticulum (ER) resident protein primarily expressed in neuroendocrine tissues including the adrenal medulla, brain, pancreas, pituitary, and pancreatic islets 1. The protein localizes to the ER lumen through a unique mechanism involving proteolytic degradation in a post-ER pre-Golgi compartment, which prevents its normal secretion and maintains its ER residence 2. RESP18 shares sequence homology with the luminal domain of IA-2/PTPRN and is found within dense core vesicles of pancreatic islet cells, where it binds insulin and proinsulin with high affinity 34. The protein's expression is regulated by glucose, dopamine, glucocorticoids, and insulin, with elevated levels observed in diabetic conditions 13. RESP18 appears to play important roles in cellular stress responses, as it is involved in dopaminergic neurotoxin-induced cell death and ER stress pathways 5. Genetic studies have identified RESP18 variants associated with amyotrophic lateral sclerosis, diabetic kidney disease, and non-syndromic cleft lip and palate, suggesting broader roles in disease pathogenesis 678.