Islet-2 (ISL2) is a LIM/homeodomain-type transcription factor that plays a crucial role in various developmental processes, particularly in the nervous system and pancreas. It is expressed in embryonic zebrafish and is involved in the differentiation of neurons and the regulation of gene expression. ISL2 is also implicated in the regulation of metabolic pathways and immune responses, and its expression is associated with diseases such as Fraser Syndrome 1 and AMME Complex. In pancreatic islets, ISL2 has been shown to be involved in the regulation of insulin secretion and β-cell function. Additionally, ISL2 has been identified as a potential tumor suppressor in pancreatic cancer, where its epigenetic silencing can reprogram the metabolism of cancer cells, leading to increased oxidative phosphorylation and sensitivity to mitochondrial complex I inhibitors.