14-3-3 protein gamma

14-3-3 protein gamma (YWHAG) is an adapter protein that regulates diverse signaling pathways through phosphoserine/phosphothreonine motif recognition on partner proteins (UniProt: P61981). It modulates binding partner activity and participates in NMDA receptor regulation, mitochondrial protein degradation, and cell adhesion processes. The protein is ubiquitously expressed across tissues.

In the central nervous system, 14-3-3 protein gamma is implicated in epileptic encephalopathy; mutations cause developmental and epileptic encephalopathy 56 (DEE56, autosomal dominant) (UniProt: P61981). Beyond this monogenic condition, the protein's roles in glutamate signaling and neuronal protein quality control position it within neurodegenerative disease pathways.

In Alzheimer's disease, 14-3-3 protein gamma is significantly downregulated in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of −1.62 across subcellular fractions (Chaparral AD proteomics). This reduction may reflect disrupted adapter function in mitochondrial and synaptic signaling cascades characteristic of AD pathology.