Chromogranin

Chromogranin is a family of acidic secretory proteins produced by neuroendocrine cells. The term most often refers to chromogranin A (CgA), a member encoded by the CHGA gene, but the family also includes chromogranin B (CgB) and chromogranin C, with CHGB and CHGC genes. These proteins are co-stored with catecholamines in dense-core secretory granules of neuroendocrine and some neuronal cells and are released in response to secretory stimuli.

Chromogranin A is a large acidic protein that acts as a prohormone and a precursor to multiple smaller bioactive peptides. Proteolytic processing yields peptides such as vasostatin and catestatin, among others, which have vasodilatory, immunomodulatory, or metabolic effects. Through active processing, chromogranins participate in regulation of cardiovascular function and energy metabolism, though the precise in vivo roles are complex and context-dependent.

Clinical significance: Measurement of CgA levels in blood or plasma is used as a biomarker for neuroendocrine tumors (NETs), including pheochromocytoma and carcinoid tumors, and can aid in diagnosis or monitoring of disease burden and treatment response. Immunohistochemical staining for CgA is widely used to demonstrate neuroendocrine differentiation in tumors. However, CgA levels can be elevated in non-neuroendocrine conditions such as chronic kidney disease, inflammatory states, and hepatic disease, and can be increased by proton pump inhibitor therapy; interpretation requires clinical context and, ideally, multiple lines of evidence.

Chromogranin B and related granin family proteins are also found in secretory vesicles and share diagnostic utility, though CgA remains the most commonly used clinical marker. Historical context: Chromogranin was first discovered in chromaffin granules in the adrenal medulla in the 1960s.