INSR encodes a receptor tyrosine kinase that mediates insulin's pleiotropic metabolic and growth-promoting actions. Upon insulin binding, INSR undergoes autophosphorylation and phosphorylates intracellular substrates including IRS proteins, which serve as docking sites for SH2 domain-containing proteins like PI3K and SHP2 1. This activation triggers two principal signaling cascades: the PI3K-AKT pathway, which promotes glucose transporter translocation to facilitate glucose uptake and regulates gluconeogenic and lipogenic gene expression through FOX transcription factors; and the Ras-MAPK pathway, which mediates cell growth and differentiation 1. INSR also binds insulin-like growth factors I and II with variable affinity depending on receptor isoform composition. Dysregulation of INSR signaling is implicated in type 2 diabetes, where insulin resistance involves defects in proximal signaling components 2. Loss of inceptor, an INSR inhibitor, increases β-cell INSR-IGF1R activation, enhancing β-cell proliferation and improving glucose tolerance, suggesting INSR sensitization as a diabetes therapeutic target 3. Clinical relevance includes monogenic diseases (leprechaunism, Rabson-Mendenhall syndrome) and associations with polycystic ovary syndrome, where INSR variants correlate with hyperinsulinemia and metabolic dysfunction 4. Emerging evidence links hyperinsulinemia to cancer progression through maintained INSR signaling in malignant cells 5.