Abstract Universities are expected to play a proactive role in the sustainable development and transformation of their regions. However, they face external and internal barriers to play that role. One possible approach to overcome those barriers is through transformative academic institutions (TAIs). TAIs are defined as research centres created within universities to proactively engage in territorial development processes and can act as ‘living labs’ from which universities can draw lessons when developing a regionally engaged role. The article explores the TAI concept further by posing the following research question: How does the TAI approach look like in different contexts? What factors support and/or hinder TAI development? To that end, we analyse the case of five academic partners working in different organisational research settings within larger university structures. Our exploration of TAI practices followed an action research approach with participatory design methods to identify commonalities, challenges, and opportunities. Findings point to a more strategic partnering with external (non-academic) actors to contribute to (longer-term) change processes that address regional sustainability challenges. This can take universities towards new roles in curating collective knowledge and catalysing and facilitating change.