Dynamic insulin secretion and glucose homeostasis are dependent on the appropriate maturation and function of pancreatic β-cells. The islet-enriched musculoaponeurotic fibrosarcoma oncogene family A (MAFA) transcription factor acts as a master regulator of β-cell identity and function, coordinating gene expression networks required for glucose-stimulated insulin secretion. Dysregulation of MAFA contributes to β-cell dysfunction, as reduced expression is detected early in the pathogenesis of Type 1 Diabetes and Type 2 Diabetes, while long-lived variants can drive monogenic forms of diabetes. In this review, we summarize the current understanding of MAFA on β-cell maturation and function in both the mouse and human. This includes structural features of the MAFA protein, regulation of MAFA transcription, post-translational modifications, and emerging areas of research for therapeutic potential.