Cho and colleagues investigated the role of DARPP-32 in Alzheimer's disease (AD), and found that DARPP-32 is cleaved at Thr-153 by calpain, which reduces the phosphorylation of cAMP-response element-binding protein (CREB), a target of PP1 and important for cognitive function. Here, PPP1R1B is linked to early-onset autosomal dominant Alzheimer disease.