Abstract: Pancreatic acinar cells exhibit high plasticity and can transdifferentiate into duct-like progenitor cells, a process known as acinar-to-ductal metaplasia (ADM). ADM plays a critical role in pancreatic injury repair and the development of exocrine pancreatic diseases. Although ADM is a reversible regenerative process, it may lead to pancreatic intraepithelial neoplasia (PanIN) and eventually progress to pancreatic ductal adenocarcinoma (PDAC) under persistent inflammation or oncogenic stimulation. Since pancreatic cancer is often diagnosed at an advanced stage, elucidating its underlying mechanisms is crucial for the development of early diagnostic markers and intervention strategies. This review summarizes the regulatory mechanisms of acinar cell transdifferentiation and its functions in exocrine pancreatic diseases.