Members of the BTB-kelch super family play important roles during fundamental cellular processes such as the regulation of cell morphology, migration, and gene expression. The BTB-kelch protein LZTR-1 is deleted in the majority of DiGeorge syndrome patients and is believed to act as a transcriptional regulator. However, functional and expression profiling studies of LZTR-1 have not been performed thus far. Therefore, we examined subcellular localization and function of LZTR-1 to gain insights into its biological role. Analysis of the primary structure of the protein revealed 6 N-terminal kelch motifs and two BTB/POZ domains at the C-terminus within LZTR-1. Confocal analysis of the subcellular distribution of LZTR-1 using the Golgi markers GM130, Golgin-97 and TGN46 identified a localization of LZTR-1 exclusively on the cytoplasmatic surface of the Golgi network that is mediated by its second BTB/POZ domain. In contrast to most other BTB-kelch proteins, LZTR-1 did not co-localize with actin. Treatment with Brefeldin A did not lead to LZTR-1’s redistribution to the endoplasmatic reticulum, but caused its re-localization in dispersed, punctuated structures which were also positive for GM130. These data demonstrate that LZTR-1 is a Golgi matrix- associated protein. Upon induction of apoptosis, LZTR-1 was phosphorylated on tyrosine residues and subsequently degraded, which could partially be rescued by the addition of the caspase inhibitor zVAD-fmk and the proteasome inhibitor lactacystin and MG132. Taken together, our experiments identify LZTR-1 as the first BTB-kelch protein that exclusively localize to the Golgi network that is mediated by its second BTB/POZ domain.