Intraneuronal fibrillary tangles are a major hallmark of several neurodegenerative diseases including Alzheimer's disease. The major constituents of these hallmarks are hyper-phosphorylated tau. In this study we used a neuronal cellular model which over-expresses transcription factor STOX1A in combination with the longest human tau isoform to test the effect of STOX1A on tau phosphorylation. Our results show that STOX1A induces phosphorylation of the longest human tau isoform at phospho-epitopes typically found in neurofibrillary tangles in Alzheimer's disease. In conclusion, our results show a STOX1A-dependent effect on tau phosphorylation found in neurodegenerative diseases such as Alzheimer's disease. © 2012 Elsevier Ireland Ltd.