CALB1 encodes calbindin, a calcium-binding protein with critical roles in neuronal function and disease pathology. As a cytosolic calcium buffer 1, calbindin regulates calcium homeostasis in neurons and influences neuronal firing patterns essential for cognition. In prefrontal cortex layer III pyramidal cells vulnerable to cognitive disorders, CALB1 is coexpressed with calcium-regulatory proteins including L-type calcium channels (CACNA1C), NMDA receptors (GRIN2B), and SK3 potassium channels concentrated in dendritic spines 1. CALB1-positive striatonigral neurons promote locomotion through dopamine modulation, opposing KREMEN1+ neurons that suppress movement 2. In the nucleus of the solitary tract, Calb1+ neurons are critical for nausea and retching responses to emetic toxins 3. Clinically, CALB1 dysfunction associates with neuropsychiatric vulnerability; loss of calbindin with age and inflammation correlates with Alzheimer tau pathology 1, and Calb1-negative neurons show enhanced tau accumulation in hippocampal CA1, impairing temporal memory 4. In cancer, ectopic CALB1 expression driven by human endogenous retroviruses promotes lung cancer progression by preventing senescence, though later suppresses tumor-promoting inflammation 5. CALB1 silencing enhances prostate cancer radiosensitivity via calcium dysregulation and mitochondrial dysfunction 6, suggesting therapeutic potential as a treatment target.