Midnolin has emerged as a versatile protein involved in gene regulation, metabolism and disease. It controls Early Response Genes by promoting their ubiquitin-independent proteasomal degradation. It also affects glucose metabolism by interacting with glucokinase in pancreatic beta cells. Recent studies have highlighted the significant role of Midnolin in various human diseases, including non-alcoholic fatty liver disease, Parkinson's disease, and several malignancies such as liver cancer, breast cancer, gastric cancer, multiple myeloma and B-cell leukemias and lymphomas. Moreover, it has also been linked to lipid metabolism, mitochondrial function and tumor growth. However, its exact role is still not fully understood. This review summarizes current knowledge about Midnolin functions and highlights its potential target for future research in health and disease.