The GlpG rhomboid protease from E. coli is a well-characterized intramembrane protease that cleaves trans-membrane substrates inside the lipid bilayer. Most studies have focused on the GlpG transmembrane domain containing the catalytic site, while the full-length protein, also containing a soluble cytoplasmic domain, a linker region, and a small positively charged C-terminal fragment, remains poorly understood. In this work, we used coarse-grained molecular dynamics (CGMD) simulations to investigate full-length GlpG embedded in a native-like model of the E. coli membrane. We identified differences in the distribution and clustering of phosphoglycerol(PG)-based lipids around GlpG in both leaflets depending on whether the soluble regions are present or absent. These data suggest a possible role of the cytoplasmic extensions of GlpG in the regulation of the lipid environment around GlpG, which may influence the activity of GlpG in vivo.