Delta-Notch signaling is a universal cell-cell communication pathway crucial for numerous developmental and physiological processes. Several proteins interact with and regulate the Notch pathway, including the E3 ubiquitin ligase Neuralized (Neur) that influences the stability and activity of Notch ligands. In mammals there are two homologs of Neur, Neur1 and Neur2, that both can interact with Notch ligands Delta-like1 and Jagged1. Here, we show that Neur2, in contrast to Neur1, is highly expressed during embryonic development of the brain and several non-neural tissues and its mRNA levels subside postnatally. In the hippocampal neurons of the adult brain Neur2 transcripts, in contrast to Neur1, are excluded from the dendrites. Neur2 protein has a predominantly cytoplasmic localization. We also show that in Neur1 and Neur-2 interact with another Notch ligand, Delta-like4. addition to Delta-like1, (C) 2009 Elsevier Inc. All rights reserved.