Two questions remain in most cases: 1) Is TAU a bystander, protective (like in NPC and possibly TBI) or a driver of disease (like in AD and PD), and 2) Do the disease-causing genetic abnormalities in secondary tauopathies (such as LRRK2 in PD or HTT in HD) have a direct effect on the physiology of TAU protein, and if so what is the pathomechanistic link? The gene discussed is LRRK2; the disease is Alzheimer disease.