Objective:Secreted modular calcium-binding proteins (SMOCs) are extracellular glycoproteins of the secreted protein,acidic,and rich in cysteine-related modular calcium-binding protein family and include two isoforms,SMOC1 and SMOC2,in humans.Functionally,SMOCs bind to calcium for various cell functions.In this review,we provided a summary of the most recent advancements and findings of SMOC1 and SMOC2 in development,homeostasis,and disease states.Data sources:All publications in the PubMed database were searched and retrieved (up to July 24,2019) using various combinations of keywords searching,including SMOC1,SMOC2,and diseases.Study selection:All original studies and review articles of SMOCs in human diseases and embryo development written in English were retrieved and included.Results:SMOC1 and SMOC2 regulate embryonic development,cell homeostasis,and disease pathophysiology.They play an important role in the regulation of cell cycle progression,cell attachment to the extracellular matrix,tissue fibrosis,calcification,angiogenesis,birth defects,and cancer development.Conclusions:SMOC1 and SMOC2 are critical regulators of many cell biological processes and potential therapeutic targets for the control of human cancers and birth defects.