“…Indeed, intrinsically disordered proteins, including tau, are known for their unique structural plasticity, conformational adaptability, and binding promiscuity enabling their involvement in diverse signaling roles (Uversky, 2015 ; Brandt et al, 2020 ). Interestingly, there is a clear evolutionary increase in disorder within the amino-terminal region of tau that likely enabled the development of novel protein-protein interactions (Trushina et al, 2019 ). It is noteworthy that, despite being categorized as an intrinsically disordered protein, tau is known to adopt specific folded conformations as a soluble protein (e.g., global hairpin folding; Jeganathan et al, 2006 ) and in the context of pathology (as identified by conformation-specific antibodies such as Alz50 or MC1; Wolozin et al, 1986 ; Carmel et al, 1996 ; Jicha et al, 1997 , 1999 ).…”