One of the main post-translational modifications which tau protein undergoes during neurodegeneration is its endogenous proteolysis, with two truncations described at carboxyl terminal domain (Asp421 and Glu391 truncations). Using in vitro cell models, it has been found that the expression of these truncated tau species produces morphological and functional alterations on different intracellular organelles. Recently a third truncation at carboxyl terminal of tau was described in the neuropathology by Caspase-2 proteolysis at Asp314 residue; however, its possible cytotoxic effects are still unknown. In the present project, the plasmids for Tau 315-441 were generated and expressed in the SH-SY5Y neuronal cell line to evaluate their endogenous protein expression by mass spectrometry. Tau 315-441 induced under-expression of proteins and altering membrane and nuclear proteins expression that participate in signalling pathways, control of the cell cycle and repair of the DNA.