The article reviews the proposed mechanisms of tau in traumatic brain injury (TBI), Alzheimer’s disease (AD), and epilepsy. Tau, a neuronal protein crucial for axonal transport and microtubule dynamics, can be released extracellularly in tauopathies, leading to decreased neuronal stability and neurofibrillary tangles (NFTs). The relationship between tau and inflammation is complex, with inflammatory proteins modulating cell death and neurotransmission. In TBI, AD, and epilepsy, tau is involved in excitotoxicity, ER stress, and inflammatory signaling. The authors propose that tau phosphorylation initially acts as a neuroprotective response to seizures or TBI, but if not effectively treated, it can become chronically activated, leading to a "tipping point" where tau phosphorylation transitions from neuroprotective to injurious. They also discuss the role of amyloid beta (Aβ) as a "last ditch effort" to revert the cell to programmed death signaling, and the potential for therapeutic intervention in these conditions.The article reviews the proposed mechanisms of tau in traumatic brain injury (TBI), Alzheimer’s disease (AD), and epilepsy. Tau, a neuronal protein crucial for axonal transport and microtubule dynamics, can be released extracellularly in tauopathies, leading to decreased neuronal stability and neurofibrillary tangles (NFTs). The relationship between tau and inflammation is complex, with inflammatory proteins modulating cell death and neurotransmission. In TBI, AD, and epilepsy, tau is involved in excitotoxicity, ER stress, and inflammatory signaling. The authors propose that tau phosphorylation initially acts as a neuroprotective response to seizures or TBI, but if not effectively treated, it can become chronically activated, leading to a "tipping point" where tau phosphorylation transitions from neuroprotective to injurious. They also discuss the role of amyloid beta (Aβ) as a "last ditch effort" to revert the cell to programmed death signaling, and the potential for therapeutic intervention in these conditions.