Our study highlights the complexity of the TGFβ superfamily, emphasizing the importance of dimerization patterns among its 33 members. Notably, TGFβ2 and TGFβ3, considered so far to function exclusively as homodimers, exhibit instead a strong preference for heterodimerization driven by their pro-domain specificities. This TGFβ2/3 heterodimer emerges as a key physiological regulator of skeletal muscle regeneration and tissue homeostasis.

A comprehensive understanding of TGF-β superfamily dimerization mechanisms holds promise for targeted therapeutic interventions and the development of novel strategies to modulate cellular responses in various myopathophysiological conditions.