YWHAE gene product belongs to the 14-3-3 family of proteins which mediate signal transduction by binding to phosphoserine-containing proteins. This highly conserved protein family is found in both plants and mammals, and this protein is 100% identical to the mouse ortholog. It interacts with CDC25 phosphatases, RAF1 and IRS1 proteins, suggesting its role in diverse biochemical activities related to signal transduction, such as cell division and regulation of insulin sensitivity. It has also been implicated in the pathogenesis of small cell lung cancer. YWHAE-FAMZZ fusions involved in endometrial stromal sarcoma, kidney sarcoma, and rearranged in breast cancer. Endometrial stromal sarcoma (ESS) is a genetically heterogenous group of uterine sarcomas, of which almost half are associated with JAZF1 rearrangement. Tumors with YWHAE-FAM22 rearrangements constitute a distinct group of ESS, which is associated with high-grade morphology and aggressive clinical behavior compared to JAZF1 ESS.