S100B is a calcium- and zinc-binding protein highly expressed in astrocytes, constituting one of the brain's most abundant soluble proteins 1. It functions as a multifaceted molecule with distinct physiological and pathological roles. Mechanistically, S100B binds calcium and zinc through separate high-affinity sites on each monomer 1, and mediates calcium-dependent regulation of physiological processes through interactions with target proteins 2. The protein acts as a neurotrophic factor promoting astrocytosis and axonal proliferation, and regulates sympathetic innervation of adipose tissue 1. Clinically, S100B serves as a recognized biomarker of neural distress with concentrations in biological fluids reflecting active neuropathology 3. Elevated S100B levels correlate with disease progression in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, traumatic brain injury, and epilepsy 3. Beyond neurological disorders, S100B involves myocardial pathophysiology 4 and mediates immune system crosstalk through CD8+ T cell and NK cell secretion 5. Importantly, S100B functions as a damage-associated molecular pattern molecule; experimental evidence demonstrates that overexpression worsens disease presentation while deletion ameliorates symptoms across multiple disorders 3, suggesting S100B's role extends beyond biomarker to active pathogenic contributor. S100B gene polymorphisms associate with spatial cognitive abilities in both healthy individuals and schizophrenia patients 6, indicating involvement in prefrontal function.