RCN2 (reticulocalbin 2) is an endoplasmic reticulum-localized calcium-binding protein with diverse physiological and pathological roles. Primary function: RCN2 serves as a precursor for Raptin, a sleep-induced hypothalamic hormone that suppresses appetite and promotes weight loss 1. RCN2-expressing neurons in the paraventricular nucleus release Raptin during sleep in a circadian pattern regulated by vasopressin-expressing neurons, which binds glutamate metabotropic receptor 3 (GRM3) to inhibit appetite via PI3K-AKT signaling 1. RCN2 nonsense variants cause night eating syndrome and obesity in humans 1. Mechanism in disease: Beyond appetite regulation, RCN2 functions as an oncogenic driver across multiple cancer types. In hepatocellular carcinoma, RCN2 promotes proliferation by interacting with EGFR and enhancing the EGFR-ERK pathway 2. In esophageal squamous cell carcinoma, RCN2 facilitates metastasis and cisplatin resistance by mediating PPP2CA ubiquitination and degradation through UBR5, activating PI3K-AKT signaling 3. RCN2 also promotes vascular calcification through a STAT3/miR-155-5p feedback loop 4 and contributes to atherosclerosis by driving oxidized lipid-induced cytokine production 5. Clinical significance: Elevated RCN2 expression correlates with poor prognosis in colorectal cancer and hepatocellular carcinoma 62. Circulating RCN2 serves as a potential biomarker for atherosclerosis and coronary/peripheral artery disease 5. RCN2 represents a promising therapeutic target for multiple malignancies and metabolic disorders.