Multiple reports indicate that a recombinant ErbB4 cytoplasmic domain functions as a tumor suppressor, suggesting that cleavage of the native ErbB4 protein by Tumor Necrosis Factor alpha Converting Enzyme (TACE) and/or gamma-secretase and release of the ErbB4 intracellular domain (4ICD or s80 fragment) from the plasma membrane are required for ErbB4 tumor suppressor activity [35, 45–50]. This evidence concerns the gene ERBB4 and neoplasm.