In Mass Effect 2, when Commander Shepard and the crew of the Normandy SR-2 launched their assault on the home base of the Collectors, they encountered at its heart a Reaper that was still in the early stages of construction. This Reaper did not share the cuttlefish-style appearance of Reaper capital ships, instead resembling the upper portion of a human skeleton. The Collectors had harvested thousands of humans they had abducted from colonies across the Terminus Systems, breaking them down into raw material to construct a new Reaper.

Though incomplete, the Human-Reaper larva was very much alive. It attacked Shepard's team by attempting to crush them beneath its arms and by firing magnetically-charged hydrodynamic blasts from its mouth. Collector soldiers under the control of the Reaper Harbinger would also fly in to protect the larva. However, the Normandy crew were successful in terminating the larva by targeting the power nodes in the chest and eye sockets. Though Shepard succeeded in destroying the Collector base, much of its technology - including the Proto-Reaper's corpse - remained intact and was later salvaged by the human supremacist group Cerberus. Using the technology harvested from the Collector base, the Illusive Man had all of his troops cybernetically modified. Due to the Proto-Reaper's proximity, however, the Illusive Man fell victim to Reaper indoctrination and led Cerberus into fighting against the Human Systems Alliance and its allies during the Reaper War in Mass Effect 3.

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