MAPK8 and amyotrophic lateral sclerosis: Threonine175 (Thr175) is one of the important phosphorylation sites in tau protein that was first identified in AD[47] and then in amyotrophic lateral sclerosis (ALS) with cognitive impairment (ALSci).[48,49,50,51,52] This modification site can be phosphorylated by multiple kinases related to tauopathy, including GSK3β, JNK, ERK2, and p38,[53] that induce tau aggregation.[54] pThr175 tau induces GSK3β activation and can augment tau phosphorylation at Thr231 and other residues.