Objective:To provide a comprehensive literature review on roles of coagulation factor ⅩⅢ (FⅩⅢ) in coagulation,wound healing,neoplasm,bone metabolism,and pregnancy.Data Sources:All articles in PubMed with key words Coagulation factor ⅩⅢ,wound,leukemia,tumor,bone, and pregnancy with published date from 2001 to 2016 were included in the study.Frequently cited publications before 2000 were also included.Study Selection:We reviewed the role of FⅩⅢ in biologic processes as documented in clinical,animal,and in vitro studies.Results:FⅩⅢ,a member of the transglutaminase (TG) family,plays key roles in various biological processes.Besides its well-known function in coagulation,the cross-linking of small molecules catalyzed by FⅩⅢ has been found in studies to help promote wound healing,improve bone metabolism,and prevent miscarriages.The study has also shown that FⅩⅢ concentration level differs in the blood of patients with leukemia and solid tumors and offers promises as a diagnostic indicator.Conclusions:FⅩⅢ has many more biologic functions besides being known as coagulation factor.The TG activity of FⅩⅢ contributes to several processes,including wound healing,bone extracellular matrix stabilization,and the interaction between embryo and decidua of uterus.Further research is needed to elucidate the link between FⅩⅢ and leukemia and solid tumors.