Here, we identified a novel TGFβ1-HS3ST2-tau signaling axis involved in tau pathology and synaptic impairment.<h4>Methods</h4>We used primary hippocampal neurons from a transgenic mouse model of tauopathy to investigate the relevance of TGFβ1 signaling on <i>Hs3st</i> expression and tau pathology. The gene discussed is TGFB1; the disease is tauopathy.