INS-IGF2 is a readthrough fusion transcript composed of exons from the upstream INS gene and downstream IGF2 gene on chromosome 11.5, with expression primarily restricted to pancreatic beta cells 1. This chimeric transcript encodes a protein containing the preproinsulin signal peptide, insulin B-chain, eight amino acids of the C-peptide, and 138 amino acids from IGF2 1, enabling insulin receptor binding and growth factor activity. INS-IGF2 expression is regulated by the INS-IGF2-H19 imprinting control region and shows tissue-specific, imprinted expression patterns 2. The transcript exists in multiple splice variants with possible viral regulation in liver tissue 3. Clinically, INS-IGF2 dysregulation associates with multiple diseases. In type 1 diabetes, INS-IGF2 serves as an autoantigen, with elevated autoantibodies in newly diagnosed patients sharing epitopes with insulin 1. In Wilms tumor, increased INS-IGF2 expression correlates with disease relapse and poor prognosis 4. Insulinomas show remarkably elevated INS-IGF2 expression compared to normal pancreatic tissue, suggesting neoplasia-specific upregulation useful as a biomarker 5. Additionally, dysregulation of the related miR483 microRNA embedded within IGF2 causes growth restriction and metabolic dysfunction through IGF1 repression 6. These findings establish INS-IGF2 as a metabolic and immunological regulator with significant pathological implications.