NNAT (neuronatin) is an imprinted gene with critical roles in nervous system development and metabolic regulation 1. Primarily functioning in brain development and pituitary maturation 2, NNAT localizes to the endoplasmic reticulum and lysosomes where it regulates calcium homeostasis through ORAI channel interaction 3. The protein demonstrates a strong predisposition to misfold and form cytotoxic aggregates 1. In disease, NNAT dysfunction links to multiple pathologies. Neuronatin aggregation within cortical neurons drives Lafora disease, a fatal neurodegenerative condition, while hyperglycemia-induced accumulation destroys pancreatic beta cells in diabetes 1. NNAT expression is restricted to specialized beta cell subpopulations required for normal insulin synthesis and secretion, with differential DNA methylation controlling this heterogeneity 4. Loss of NNAT expression associates with anorexia nervosa susceptibility 5 and triggers metabolic polyphenism via HDAC-dependent beta cell hyperproliferation 6. Conversely, NNAT upregulation by oxidative stress suppresses estrogen receptor-positive breast cancer proliferation 3. As an imprinted gene, NNAT normally expresses only the paternal allele; loss of imprinting from altered DNA methylation promotes aberrant cell proliferation and metastasis 1.