The I4MS program in H2020 has been and is a great success for the Digital Transformation of European Manufacturing SMEs. Phase IV of the program was focussing on DIHs and on highly innovative technologies like Digital Twins and AI. In particular, the AI REGIO Innovation Action developed a virtuous alliance between Regions, DIHs, AI solution providers and Manufacturing SMEs, which is materialised by a new methodology for DIHs service portfolio and customer journey analysis, an AI4EU -oriented toolkit of Data and AI resources, a network of Didactic Factories and their TEchnology and REgulatory SAndboxes (TERESA) and an ecosystem of SME-driven experiments and their Digital Transformation pathways. It is time now to align such important outcomes to the evolution of Manufacturing towards Industry 5.0, the evolution of cloud AI Technologies to AI-at-the-Edge, the evolution of H2020 to Horizon and Digital Europe programmes e.g. to EDIH, Data Spaces and AI TEFs (Testing and Experimentation Facilities) for Manufacturing. Some of the AI REGIO I4MS Phase IV motivations are now evolved: it is time for AI REDGIO 5.0 for keeping momentum of AI technologies adoption in Manufacturing SMEs. AI REDGIO 5.0 aims at renovating and extending the H2020 I4MS AI REGIO alliance between Vanguard EU regions and DIHs for a competitive AI-at-the-Edge Digital Transformation of Industry 5.0 Manufacturing SMEs. AI REGIO outcomes (methods and tools for DIHs governance and cross-DIH collaboration; Data Space and AI for Manufacturing toolkit; Didactic Factories network and TERESA facilities; SME-driven experimentations in 14 Vanguard regions) will be i) extended to the I5.0 principles; ii) enabled by the newest trusted technologies along the edge-to-cloud continuum; iii) supported by European open source hw/sw reference implementations, preserving EU values and ethical principles; iv) interconnected with the EDIH network in DEP as well as with the AI TEF nodes and the Data Spaces deployment program.