Ret

The Ret family, represented in humans by a single gene, RET, encodes a receptor tyrosine kinase with a distinctive modular ectodomain: four cadherin-like repeats and a cysteine-rich region, followed by a single transmembrane helix and a cytoplasmic kinase domain. RET does not bind its GDNF-family ligands directly; instead, ligand engagement of GPI-anchored GFRα co-receptors assembles the active receptor complex. RET is essential for enteric nervous system colonization, kidney organogenesis and spermatogonial stem cell maintenance. Loss-of-function variants cause Hirschsprung disease, while activating mutations or fusions drive multiple endocrine neoplasia type 2, medullary and papillary thyroid carcinoma and lung adenocarcinoma, establishing RET as both developmental gene and clinical oncology target.