CALB2 (calbindin 2) encodes calretinin, a calcium-binding protein that functions as a cytosolic calcium buffer to modulate intracellular calcium signaling and homeostasis 1. The protein affects both temporal and spatial aspects of transient calcium increases and plays a role in precise regulation of calcium signaling 1. CALB2 is involved in inhibitory neurotransmission, spatial learning, and neural plasticity in the brain 2. The gene is chr16 located at 16q22-q23, suggesting evolutionary duplication with carbonic anhydrase genes 3. In pathological contexts, CALB2 demonstrates significant disease relevance across multiple cancer types. In pancreatic ductal adenocarcinoma (PDAC), CALB2 drives metastasis through inflammatory reprogramming of the tumor microenvironment, collaborating with hypoxia to activate cancer-associated fibroblasts and promoting the Ca2+-CXCL14 inflammatory axis 4. CALB2 also facilitates M2 macrophage polarization in pancreatic adenocarcinoma, promoting tumor growth and metastasis 5. Additionally, CALB2 serves as a biomarker for severe carotid artery stenosis and shows enrichment in mast cells within atherosclerotic plaques 6. A polymorphism in CALB2 intron 9 (SNP513) represents a risk factor for colon cancer development 7.