Three diverse projects have recently converged in our institute, which have taken different approaches to an old problem of understanding cancer and wound healing. The first study looked at epidermolysis bullosa simplex (EBS), a very rare, incurable, skin fragility disorder caused by mutations in keratin intermediate filament proteins, and carrying an increased risk of basal cell carcinoma. We set out to investigate the downstream consequences of mutant keratin expression, in the search for an entry point for cheaper therapeutic approaches to rare diseases like these. Cell models were generated expressing wild-type and mutant keratin proteins coupled to GFP and used for live cell imaging. When these cells were subjected to stress in tissue culture, it emerged that the constitutive stressed state of these mutant cells can mimic stresses such as wounding, raising questions about the wound signals that initiates keratinocyte migration in vivo. An unrelated study on rare inherited self-healing keratoacanthomas had recently focused our attention on TGFbeta signaling, known to be essential for wound healing. When TGFBR1 receptor was lost, individuals became susceptible to multiple self-healing squamous epithelioma (MSSE). Meanwhile a third study, using the culture wounding model systems set up for EBS, has now uncovered a unique miRNA switch mechanism by which TGFbeta signaling triggers wound healing migration in keratinocytes, and fails to do so in diabetic wounds. The unexpected synergy between these projects has demonstrated how studies on rare diseases can better position us to learn about more common medical challenges.