GRB10 is an adapter protein that primarily functions as a negative regulator of insulin and insulin-like growth factor signaling. It suppresses activated receptor tyrosine kinases through two mechanisms: interference with signaling pathways and increased receptor degradation 1. Specifically, GRB10 blocks association between the insulin receptor (INSR) and adapter proteins IRS1/IRS2, preventing their tyrosine phosphorylation and delaying AKT1 activation 2. GRB10 recruits NEDD4 to IGF1R, promoting receptor ubiquitination and degradation 1. Additionally, GRB10 negatively regulates Wnt signaling through LRP6 interaction while positively regulating VEGFR-2 signaling 3. Clinically, GRB10 variants are associated with type 2 diabetes risk in a parent-of-origin-dependent manner, with paternal inheritance increasing diabetes susceptibility while maternal inheritance paradoxically reduces fasting glucose 2. GRB10 is subject to genomic imprinting in a tissue-specific manner, influencing both metabolic homeostasis and potentially adult behavior 4. In renal cell carcinoma, altered GRB10 promoter methylation correlates with aggressive disease phenotypes and metabolic reprogramming 5. These findings highlight GRB10's crucial role in glucose metabolism, growth regulation, and disease pathogenesis.