Reticulocalbin-2 (RCN2)

Reticulocalbin-2 (RCN2) is a calcium-binding protein localized in the lumen of the endoplasmic reticulum (ER). It contains six conserved EF-hand motifs, some of which bind calcium ions, and is thought to regulate Ca2+-dependent processes within the ER or post-ER compartments. RCN2 is abundantly expressed in endothelial and adventitial layers of arteries and is significantly upregulated in atherosclerotic lesions in both humans and animal models. It plays a role in basal and lipid-induced cytokine production in vascular wall cells, suggesting a function in regulating vascular inflammation and cardiovascular disease pathogenesis. Circulating RCN2 levels are elevated in patients with coronary artery disease and peripheral artery disease and inversely correlate with protective HDL cholesterol levels, which also downregulates RCN2 expression in endothelium. Genetic associations link RCN2 with Bardet-Bbl syndrome and developmental epileptic encephalopathy. No approved pharmaceuticals act directly on RCN2, but its expression is modulated by HDL and statin treatment, implicating a possible indirect therapeutic link. RCN2 is proposed as a novel non-invasive biomarker for atherosclerosis, but systematic investigation of its safety, clinical utility, and direct pharmacological targeting is still lacking.

Other names

Reticulocalbin-2RCN2ERC55E6BPERC-55TCBP49Calcium-binding protein ERC-55E6-binding proteinreticulocalbin 2EF-hand calcium binding domain (endoplasmic reticulum calcium-binding protein, 55kD)

Not targeted by approved drugs as a primary mechanism; HDL and statins suppress RCN2 expression, contributing to anti-atherosclerotic and anti-inflammatory effects