NELL2 is a neuron-specific secreted glycoprotein containing in N-terminal thrombospondin I-like domain (TSP-N) In this study. we describe NELL2-Tsp, a novel alternative splice variant of rat NELL2 NELL2-Tsp uses an alternate stop codon resulting in a C-terminal truncated form of NELL2, containing a signal peptide and a TSP-N domain NELL2-Tsp is a glycosylated protein specifically expressed In brain tissue. NELL2-Tsp and NELL2 are secreted, likely due to the putative signal peptide. However. Clue to the truncation, the secreted portion of NELL2-Tsp is smaller than that of NELL2 Immunoprecipitation analysis confirmed that NELL2-Tsp was able to associate with NELL2 and with itself In addition, expression of NELL2-Tsp notably reduced secretion of NELL2 and inhibited NELL2-mediated neurite Outgrowth These results suggest that NELL2-Tsp may act as a negative regulator of wild-type NELL2 (C) 2009 Elsevier Inc All rights reserved