Tau (phospho S396) refers to the phosphorylation of the tau protein at serine residue 396. Phosphorylation at S396 is associated with the physiological role of tau in synaptic plasticity, which is the dynamic modulation of synaptic connections and is thought to underlie learning and memory processes. Tau phosphorylation at S396 has been shown to regulate the interaction between protein kinase C binding protein 1 (PICK1) and GluA2, which is fundamental to AMPAR internalization, a key molecular mechanism of LTD. Phosphorylation at S396 also contributes to reduced tau-microtubule binding and is correlated with C-terminal tau cleavage and distinct conformational changes in the protein.