Cellular identity is fundamentally determined by the precise regulation of protein synthesis, which governs growth, differentiation, and function. In the pancreas, the balance between exocrine and endocrine cell types is critical for organ function, and the disruption of protein synthesis in these cells can lead to diseases such as exocrine insufficiency and diabetes. The specialized mRNA translation factor eukaryotic initiation factor 5A (eIF5A) has emerged as an essential regulator of on-demand protein synthesis in professional secretory cells. Here, we investigate the role of eIF5A-mediated mRNA translation in lineage specification during pancreas development. Using genetic mouse models, our studies reveal that loss of eIF5A results in a marked reduction of exocrine volume and a paradoxical expansion of the insulin-producing beta cell population. We reveal that these cellular changes are driven by impaired on-demand protein synthesis during the critical stage of pancreatic cell differentiation. Mechanistically, we show that eIF5A deficiency disrupts the synthesis of proteins critical for proper pathway signaling—most notably Notch—that instruct cell fate decisions. As a result, we observe impaired ductal branching and tip formation as well increased Ngn3+ endocrine progenitors within the ducts. These changes in lineage allocations directly contribute to decreased acinar cell and increased beta cell mass. Remarkably, eIF5A-deficient mice maintain elevated beta cell mass and exhibit preserved glucose tolerance despite severe exocrine deficiency. Collectively, our findings establish that eIF5A-mediated mRNA translation regulates critical developmental signaling pathways and reinforces the finding that disruptions in protein synthesis can reprogram cellular identity and drive disease pathogenesis.