Calprotectin, an acute phase reactant plays vital physiological roles in infection and inflammation. It serves as a potential diagnostic marker for various inflammatory diseases including Inflammatory bowel disease, Sepsis, and Necrotizing enterocolitis. Once get induced by LPS or chemokines, calprotectin is secreted predominantly by the neutrophils and is translocated to the extracellular fluid where it takes part in major biological processes like signal transduction, tumorigenesis, apoptosis, cell homeostasis and inflammation. Calprotectin acts as an endogenous ligand of TLR4 receptor and further amplifies infection and inflammation. In this article, we review the molecular structure of calprotectin and its roles in disease conditions. Genetic behavior is also an important factor in calprotectin expression and is found to be associated with disease activity. Knock down studies revealed the secrets behind the pathophysiological functions of calprotectin and suggested it as a therapeutic target for inflammatory diseases.