“…In 1979, Osteopontin (OPN) was first noticed by Senger, and in 1985 was named by Franzen [ 1 ], OPN is a Latin word osteo means bone and pontin means Bridge, which has a relation with the lusty role of OPN in the body, sometimes OPN mentioned as an early T-lymphocyte activation protein 1 [ 2 ], or secreted phosphoprotein 1 (SPP-1) [ 2 , 3 ], OPN is encoded by SPP1 gene that is a multifunctional soluble cytokine and a matrix-related glycoprotein belongs to the small integrin-binding ligand N-linked glycoprotein [ 4 , 5 ], existing in some fluids of the body such as blood, urine, and milk, and a plurality of tissues [ 6 ] and in many organs like gall bladder, kidney, lungs, breasts, brain, placenta, salivary and sweat glands, pancreas, inner ear, arteries, nerve cell, an immune cell, urinary and reproductive tracts, epithelial cells of the digestive system [ 7 , 8 ], OPN has participated in a different number of physiological processes including the organizing of bone formation/resorption, organizing of the immune system, brain and gut development [ 6 ], OPN has also a pathogenic role in atherosclerosis, tumorigenesis, metastasis, and liver inflammation and injury [ 7 , 1 ], it canchange the hepatic cholesterol metabolism thus participating in the pathogenesis of cholelithiasis in experimental animals [ 9 ], and because of its increased expression in the epithelium of intrahepatic bile stone-loaded ducts, it is closely related to hepatolithiasis [ 10 ]. However, the mechanism and role of OPN in forming cholesterol gallstone (GS) are undetermined [ 11 ].…”