Conserved proteins are characterized by their functions remaining nearly constant throughout evolutionary history, both vertically through time and horizontally across species. In this review, we focus on a class of conserved proteins known as the Muscleblind-like (MBNL) family. As RNA-binding proteins, MBNL family members interact with pre-mRNAs through evolutionarily conserved tandem zinc finger domains and play critical roles in various RNA metabolic processes, including alternative splicing, mRNA stability, trafficking, regulation of subcellular localization, and alternative polyadenylation. Dysregulation of MBNL proteins can lead to severe consequences. Initially, research primarily associated MBNL proteins with myotonic dystrophy. However, recent studies have revealed their involvement in a broad spectrum of physiological and pathological processes, such as embryonic tissue differentiation and circulatory disorders. Furthermore, the emerging role of MBNL proteins in cancer sheds light on a novel aspect of these evolutionarily ancient proteins. This review provides a comprehensive overview of the MBNL family, emphasizing its structure, the mechanisms underlying its biological functions, and its roles in various diseases.Subject terms: Muscleblind-like-like protein, RNA-binding proteins, Alternative splicing, Tumor, Myotonic dystrophy.