H-Ras, a small G protein, can activate several downstream effectors and cause diverse effects in the cell. These effects include cell cycle and gene transcription regulation. In order to produce these effects, H-Ras must localize at the plasma membrane via three lipid modifications, although its precise location, inside or outside of detergent resistant membranes (DRMs), is still being debated. Several transmembrane Ras proteins (EHR61L, EHRwt, and CHR61L) were designed to localize to the plasma membrane in a lipid-independent manner. Both EHR proteins were found, by detergent extraction, to be located outside of DRMs. Based on this localization, the question was asked if Ras would still be able to find its proper downstream effectors. EHR61L causes both transformation of 3T3 cells and differentiation of PC-12 cells, in a similar manner to normal activated H-Ras. The rates of cell and neurite growth caused by EHR61L seemed to be slower than its lipid-modified counterpart. EHRwt, while being localized in non-DRMs, does not become activated in either cell type. CHR61L was only minimally able to be detected in vivo.