The endoplasmic reticulum (ER) is the largest membrane system in eukaryotic cells and is the primary site for the biosynthesis of lipids and carbohydrates, as well as for the folding, assembly, modification, and transport of secreted and integrated membrane proteins. The ER membrane complex (EMC) on the ER membrane is an ER multiprotein complex that affects the quality control of membrane proteins, which is abundant and widely preserved. Its disruption has been found to affect a wide range of processes, including protein and lipid synthesis, organelle communication, endoplasmic reticulum stress, and viral maturation, and may lead to neurodevelopmental disorders and cancer. Therefore, EMC has attracted the attention of many scholars and become a hot field. In this paper, we summarized the main contributions of the research of EMC in the past nearly 15 years, and reviewed the structure and function of EMC as well as its related diseases. We hope this review will promote further progress of research on EMC. ER membrane complex (EMC): structure, functions, and roles in diseases. EMC is a complex comprised of nine subunits, namely EMC1-8 and EMC9 or 10. Its primary function entails serving as an insertase, facilitating the proper insertion of transmembrane domain (TMD) into the lipid bilayer. Disruption of EMC can significantly impact numerous physiological processes and contribute to the development of various diseases.image