HMGN3 (high mobility group nucleosomal binding domain 3) is a chr6-binding nuclear protein that regulates gene transcription by modulating nucleosome structure and recruiting transcription factors. The protein plays critical roles in pancreatic beta cell function, where it binds to the GLUT2 glucose transporter promoter alongside PDX1 to regulate glucose-stimulated insulin secretion 1. Loss of HMGN3 in mice impairs insulin secretion and leads to diabetic phenotypes 1. HMGN3 also contributes to DNA G-quadruplex recognition and CTCF recruitment to chr6 2. In disease contexts, HMGN3 shows altered expression patterns across multiple conditions: it is upregulated in clear cell renal cell carcinoma and associated with fatty acid metabolism reprogramming 3, promotes cholangiocarcinoma cell migration by repressing epithelial regulators through SNAI2-dependent mechanisms 4, and is downregulated in dilated cardiomyopathy where its depletion promotes cardiomyocyte apoptosis 5. Additionally, HMGN3 regulates trophoblast stem cell conversion and placental development 67. The protein's dysfunction is implicated in Huntington's disease transcriptomic alterations 8, highlighting its broad importance in cellular function and disease pathogenesis.