YWHAG encodes a 14-3-3 gamma adapter protein that regulates diverse cellular signaling pathways through phosphoserine/phosphothreonine motif recognition 1. The protein serves as a critical regulator of synaptic function and cellular metabolism, with elevated cerebrospinal fluid YWHAG levels strongly correlating with cognitive impairment in Alzheimer's disease, explaining 27% of variance in cognitive decline beyond traditional biomarkers 2. In cancer, YWHAG promotes tumor progression through multiple pathways: it activates MAPK signaling via TMOD3 regulation in bladder cancer 3 and drives lung adenocarcinoma progression through JAK2/STAT3 pathway activation 1. Pathogenic YWHAG variants cause developmental and epileptic encephalopathy 56 (DEE56), characterized by early-onset seizures, intellectual disability, and developmental delay 4. The phenotypic spectrum ranges from mild developmental delay to severe epileptic encephalopathy, with genotype-phenotype correlations emerging based on variant location 4. Zebrafish studies demonstrate that YWHAG haploinsufficiency causes reduced brain size and cardiomegaly, supporting its role in neurodevelopmental disorders 5. Seizure control can be achieved in approximately half of DEE56 patients, though intellectual disability affects 96% of cases 4.