In this chapter, we identify three distinct avenues of research on the philosophical, historical, and sociopolitical dimensions of engram research. First, we single out the need to refine philosophical understandings of memory within neuroscientific research on the engram. Specifically, we question the place of constructivist and preservationist philosophical claims on memory in the formulation of the engram concept and its operationalization in contemporary neuroscience research. Second, we delve into the received historiography of the engram claiming its disappearance after Richard Semon’s (1859–1918) coinage of the concept. Differently from this view, we underline that Semon’s legacy is still largely undocumented: Unknown are the ways the engram circulated within studies of organic memory as well as the role Semon’s ideas had in specific national contexts of research in neurosciences. Finally, another research gap on the engram concerns a socio-anthropological documentation of the factual and normative resources this research offers to think about memory in healthcare and society. Representations of memory in this research, experimental strategies of intervention into the engram, as well as their translational potential for neurodegenerative (e.g., Alzheimer’s disease) and psychiatric (e.g., post-traumatic stress disorder) conditions have not yet received scrutiny notwithstanding their obvious social and political relevance.