PEA15 is a multifunctional adaptor protein that regulates glucose homeostasis, cell cycle control, and inflammatory responses. As a protein kinase C substrate, PEA15 modulates glucose uptake by controlling SLC2A1 and SLC2A4 glucose transporter trafficking and content on the plasma membrane 1. PEA15 also inhibits apoptosis by suppressing TNFRSF6- and TNFRSF1A-mediated caspase-8 activity and blocks Ras-mediated inhibition of integrin activation while regulating ERK MAP kinase signaling. In cell cycle regulation, PEA15 functions as a tumor suppressor: ATM-dependent stabilization of PEA15 in response to DNA damage activates the G2/M checkpoint and prevents CDK6-driven cell cycle progression 2. Loss of PEA15 increases spontaneous mutagenesis and accelerates transformation, while oncogenic RAS suppresses PEA15 expression. PEA15 expression is downregulated in colon, breast, and lung cancers 2. Clinically, PEA15 overexpression is associated with insulin resistance and type 2 diabetes susceptibility. First-degree relatives of diabetic patients show two-fold higher PEA15 expression correlating with reduced insulin sensitivity 3. Additionally, elevated PEA15 expression serves as an independent prognostic biomarker for poor survival and recurrence in early-stage endometrial carcinoma 4. PEA15 also suppresses inflammatory responses by inhibiting MAPK activation and reducing pro-inflammatory cytokine production 5.