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The purpose of the NASA In-Space Production Applications (InSPA) program is to provide funding and expertise to help brilliant United States innovators and businesses traverse the technology “Valley of Death” by proving out their concepts for in-space manufactured materials and products that will ultimately be sold to customers on the Earth. Scientific and technological advances on the International Space Station (ISS) and on Earth coupled with evolving societal needs are collectively enabling InSPA-funded teams to produce data streams and advanced biological, chemical, and physical materials solutions with economic value. We report on an extraordinary year of accomplishments on the ISS and highlight top InSPA and ISS National Lab results that span historic firsts in cancer research, stem cells, crystal production, optical fiber production, drug discovery, in-space treatments with RNA therapeutics, and production of artificial retinas from space. We assert that the results have enormous potential, are transforming the space exploration ecosystem and are the “seeds” of a microgravity industrial revolution that are shaping national microgravity strategy.