The E2A gene encodes two distinct basic helix-loop-helix transcription factors, E12 and E47. E12 and E47 modulate expression of their target genes through formation of homodimers and heterodimers with other basic helix-loop-helix transcription factors. E2A proteins are thought to play critical roles in regulation of cell commitment, growth and differentiation in a range of cell types including lymphocytes, muscle cells and neurons. Emerging evidence suggests that E2A proteins also play key roles in the process of epithelial mesenchymal transition, a mechanism which contributes significantly to kidney disease progression and tumour metastasis. Further understanding of the diverse effects of E2A proteins may lead to novel therapeutic approaches to targeting important disease process.