The immediate NASA commercial application for the proposed innovation is to service government and commercial customers performing microgravity research on the ISS. Market research and workshops conducted by NASA and industry concluded that high-frequency payload return is an essential capability to drive high-volume research aboard the ISS. Biotechnology has been identified as a particularly promising domain, along with materials science. Market studies conducted by NASA and independent experts suggest that space-based biomedical and other research, which is enabled by high frequency small payload return, could be a multi-billion dollar industry. While the proposed effort is specific to application of the RED-4U to enable increased ISS utilization, the technology is readily extensible to other NASA missions. The technology is applicable to an asteroid or planetary sample return vehicle similar to Stardust, Genesis, and OSIRIS-REx; or could support sample return for long duration human exploration missions to an asteroid, Moon, or Mars. Finally, other potential NASA applications include serving as a host for suborbital payloads dropped from a high altitude balloon for short microgravity exposure times, upper atmosphere research, or hypersonic flight testing. The Non-NASA commercial applications of RED-4U parallel those of the government applications. Small payload return capability complements the business models of the emerging commercial space industry and the rapidly expanding small satellite sector. RED-4U could be used to return scientific experiment samples and other payloads from commercial orbital platforms such as those proposed by Bigelow Aerospace and Orbital Technologies, or for intermittent return from free-flying commercial transportation vehicles such as the SpaceX DragonLab, Orbital Sciences Corporation Cygnus, or the Sierra Nevada DreamChaser. Sample return is also a key element of plans of commercial companies seeking to mine the Moon or asteroids such as Moon Express, Planetary Resources, and Deep Space Industries.