Little is currently known about exactly how non-MT-associated tau becomes cytotoxic en route to its oligomerization and polymerization into neurofibrillary deposits in human tauopathies other than that (a) tau becomes a substrate for tyrosine as well as serine/threonine kinases and (b) tau undergoes progressive amino and carboxyl terminal cleavage at some point in the process. The gene discussed is MARK2; the disease is tauopathy.