It is likely that Fyn/SFK inhibition protects neurons by targeting Fyn-tau interactions rather than directly reducing the level of pY18 or nNOS, a similar finding was also reported by others.54 It is also likely that tau phosphorylation at Y18 is regulated by other kinases independent of Fyn/SFK that are also affected by seizures as the Y18 remains phosphorylated in spite of the absence of Fyn in transgenic Alzheimer’s disease models.57,84 Alternatively, SAR dosing optimization may be required to reverse the early upregulation of tau phosphorylation (Y18) in epilepsy. The gene discussed is MAPT; the disease is epilepsy.