NFATC2 and Huntington disease: Noncanonical WNT signaling activates NFAT transcription factors through Ca2+-dependent cascades.24 In this pathway, Ca2+-bound calmodulin activates calcineurin, which dephosphorylates NFAT proteins, promoting their nuclear translocation and transcriptional activation of their target genes.25 Among the five NFAT isoforms (NFATc1 ~ NFATc5), transcriptome analysis of the prefrontal cortex from HD patients revealed upregulation of NFATc2 and NFATc4 (Supplementary Fig. 7a).