EPS8 is a signaling adapter that primarily regulates actin cytoskeleton dynamics to control cellular protrusions and cell motility. Mechanistically, EPS8 functions through multiple pathways: it forms a trimeric complex with SOS1 and ABI1 to transduce signals from Ras to Rac 1, displays barbed-end actin filament capping activity when bound to ABI1, and shows actin bundling activity when associated with BAIAP2 [UniProt]. EPS8 is phosphorylated by EGFR and other receptor tyrosine kinases 2, and its protein stability is regulated through ubiquitination and lysosomal degradation mechanisms involving ITSN2 and USP4 34. In normal physiology, EPS8 regulates axonal filopodia formation, stereocilia elongation, and dendritic cell migration [UniProt]. However, EPS8 is significantly overexpressed in most malignant tumors including breast, colon, and lung cancers 56, where it promotes proliferation, invasion, and metastasis 7. Notably, EPS8 overexpression enhances DNA damage repair via ATM signaling while suppressing p53, conferring chemoresistance 6. Additionally, age-associated EPS8/RAC hyperactivation promotes pathological protein aggregation in neurodegenerative diseases like Huntington's disease and ALS 4. Mutations in EPS8 cause autosomal recessive deafness [NCBI Summary]. Given its roles in tumorigenesis and neurodegeneration, EPS8 represents a promising therapeutic target for cancer and age-related neurological diseases.