Epsin 3 (EPN3), an oncogene with prognostic and therapeutic relevance in BC, drives breast tumorigenesis by increasing endocytosis of E-cadherin, followed by the activation of a β-catenin/TCF4-dependent p-EMT and establishment of an aTGFβ-dependent autocrine loop that sustains EMT. The gene discussed is EPN3; the disease is breast cancer.