RET (Rearranged during Transfection) is a receptor tyrosine kinase that plays critical roles in embryonic development and postnatal physiology 1. The protein functions as a component of the signaling pathway activated by glial cell line-derived neurotrophic factor (GDNF) family ligands 2, with RET signaling essential for neuronal and renal organogenesis 2. Upon GDNF binding, RET undergoes dimerization and autophosphorylation, activating downstream signaling cascades including RAS/ERK, PI3K/AKT, p38 MAPK, and JNK pathways 3. RET mutations have profound clinical significance: germline activating mutations cause multiple endocrine neoplasia type 2 (MEN-2A and MEN-2B), characterized by medullary thyroid carcinoma, pheochromocytoma, and other endocrine tumors 4. Somatic RET rearrangements, particularly RET/PTC fusions and missense mutations, drive papillary thyroid carcinoma development 56. RET mutations also occur in epithelial ovarian cancer, where they activate MAPK and AKT signaling 7. Loss-of-function mutations cause Hirschsprung disease, demonstrating RET's essential role in enteric neuron development 3. Currently, 78 pathogenic RET mutations have been identified, with 91% being missense variants clustered in exons 10-11 1, making RET mutation status critical for molecular diagnostics and personalized therapeutic strategies.