ECE2 (endothelin converting enzyme 2) is a metalloendopeptidase that primarily converts big endothelin-1 to the potent vasoconstrictor endothelin-1, requiring acidic pH for optimal activity 1. The enzyme exhibits broad substrate specificity, also processing various neuroendocrine peptides including neurotensin, angiotensin I, substance P, and peptides derived from proenkephalin and prodynorphin 1. ECE2 functions in multiple cellular processes including neurogenesis and neuronal migration during cortical development, where its disruption leads to periventricular heterotopia through abnormal neural progenitor and neuron localization 2. The gene is located on chromosome 3-q29 and exists as multiple mRNA isoforms with structural diversity at the 5'-terminus 3. ECE2 plays a protective role in Alzheimer's disease by degrading amyloid-β protein, with rare coding mutations (R186C and F751S) significantly impairing this enzymatic activity and contributing to AD pathogenesis 4. The enzyme is also implicated in cancer biology, serving as a prognostic biomarker in lung adenocarcinoma and being identified as a potential driver gene in intrahepatic cholangiocarcinoma 56. Additionally, ECE2 contributes to melanoma metastatic plasticity by processing endothelin-3, promoting phenotype switching between invasive and proliferative states 7.