From wavy hair to naked proteins: The role of transforming growth factor alpha in health and disease

• TGFA is an EGFR ligand.
• TGFA surface delivery and cleavage are two important regulatory steps.
• Forced expression of TGFA acts as epithelial mitogen and carcinogen.
• TGFA interaction with NKD2 is required for its basolateral delivery.
• TGFA is dysregulated in hyper-proliferative epithelial disorders.

Since its discovery in 1978 and cloning in 1984, transforming growth factor-alpha (TGF-α, TGFA) has been one of the most extensively studied EGF receptor (EGFR) ligands. In this review, we provide a historical perspective on TGFA-related studies, highlighting what we consider important advances related to its function in normal and disease states.