NELL2 is as a neuron-specific secreted glycoprotein. The present study provides evidence of an alternatively spliced variant of the rat NELL2 gene that yields cytosolic NELL2 (cNELL2). cNELL2 was initially detected in the thymus and subsequently found to be ubiquitously expressed in many other tissues. The absence of the sequences corresponding to the third exon, which contains the terminal portion of the signal peptide, accounts for the uniform distribution of cNELL2 throughout the cytoplasm. This is in contrast to NELL2, which is preferentially located at distinct subcellular structures involved in the secretary process, such as endoplasmic reticulum and Golgi apparatus. Western blot analysis showed that cNELL2 was not present in the medium but only in lysates, while NELL2 was detected as a glycosylated larger form in both lysates and media. Immunoprecipitation analysis revealed that cNELL2 interacts with PKC beta 1. These results suggest that cNELL2 is involved in PKC beta 1-mediated intracellular signaling. (c) 2006 Elsevier Inc. All rights reserved.