PFKFB3 and Alzheimer disease: To understand how PPARγ signaling influences the metabolic phenotype of the TREM2 variants we interrogated PFKFB3 signaling, a key regulatory enzyme involved in glycolytic induction25, 26 and identified as a target of PPARγ.24 We found that pioglitazone exerted its effects via a p38MAPK/PFKFB3 signaling cascade and we show that activation of the PPARγ/p38MAPK cascade and PFKFB3 activity is sufficient to rescue the functional deficit in Aβ1‐42 phagocytosis identified in the TREM2 hypomorphic iPS‐Mg, a key hallmark associated with AD pathogenesis.