WDFY2 is a multifunctional endosomal adapter protein containing WD40 and FYVE domains that functions across multiple cellular processes. Structurally, the FYVE domain binds phosphatidylinositol 3-phosphate with high specificity 1, enabling WDFY2 localization to early endosomes and endosomal tubules 2. In metabolic signaling, WDFY2 facilitates hepatic insulin sensitivity by controlling endosomal localization of the insulin receptor and recruiting IRS1/2 to activate AKT2 signaling 3. WDFY2 also regulates adipocyte differentiation through AKT1-mediated FOXO1 inactivation 4. Beyond metabolism, WDFY2 restrains cancer cell invasion by controlling VAMP3-dependent MT1-MMP recycling; its frequent loss in metastatic cancers suggests tumor suppressor function 5. Importantly, WDFY2 promotes DNA damage repair by bridging MRE11 and NBS1 to facilitate MRN complex formation at double-strand breaks following ATM-CHK2-mediated phosphorylation 6. The CDKN2D-WDFY2 fusion occurs in 20% of high-grade serous ovarian carcinomas, altering PI3K/AKT signaling 7. Pan-cancer analysis reveals WDFY2 downregulation in most cancers, with expression correlating with immune infiltration patterns 8. These findings establish WDFY2 as a multivalent platform protein linking endosomal trafficking, insulin signaling, DNA repair, and cancer suppression.