The cost of biomass degradation enzymes is widely considered an important factor in the commercialization of lignocellulosic biomass-to-ethanol processes. The use of microorganisms in the production of enzymes is the main platform available nowadays. However, molecular farming may represent an alternative platform and tobacco constitutes an ideal system for production of recombinant enzymes due to its low cost of production and its scale-up potential. However, although production of recombinant protein in tobacco is routinely used nowadays, the level of protein expression is not sufficient for commercial production. Aiming a highly cost effective system for production of soluble sugars for cellulosic ethanol industry, we have been working on the development of transgenic tobacco lines expressing high levels of cell wall degrading enzymes (CWDE). An endoglucanase from Ruminococus albus (Cel5) and exoglucanase of Thermobifidus fusca (Cel6B) were engineered with a carbohydrate binding module (CBM6) of Clostridium stercorarium and fused to an elastin-like polypeptide (ELP), a pentapeptide repeat polymer (Val-Pro-Gly-Xaa-Gly) that has been shown to increase recombinant protein accumulation in plants. These constructs were targeted to two subcellular compartments by adding the sorting signal peptide KDEL for ER and CTPP for vacuole. After transient expression in Nicotiana benthamiana, our results revealed that fusions of Cel5::CBM6::ELP and Cel6b::CBM6::ELP, when targeted to the ER, accumulate to very low levels. In comparison, both cellulases accumulated to about 1% of total soluble protein when targeted to the vacuole. Interestingly, it has been previously reported that fusion of proteins with ELP accumulates to high levels in the ER. This result suggests that evaluation of subcellular compartmentalization is extremely important in order to maximise recombinant protein accumulation in plants.