As well as DNA-binding functions, evidence suggests that the ETS domain is also involved in protein-protein interactions.

For example, the ERG ETS transcription factor is fused to the EWS gene, resulting in a condition called Ewing's sarcoma.

[6] The fusion of TEL to the JAK2 protein results in early pre-B acute lymphoid leukaemia.

[8] In addition, ETS factors, e.g. the vertebrate Etv1 and the invertebrate Ast-1, have been shown to be important players in the specification and differentiation of dopaminergic neurons in both C. elegans and olfactory bulbs of mice.

It is thought that interactions with other proteins (eg: Modulator of the activity of Ets called Mae) is one way in which specific binding to DNA is achieved.