Durability has become a central descriptor of somatic gene-therapy performance, yet the term is frequently applied to biologically different observations. Persistent vector DNA, continued transgene expression, long-lived corrected cells, and sustained therapeutic function can coincide, but none is an automatic surrogate for the others. This conceptual framework separates these layers and examines the biological and measurement conditions under which each can support a claim of durable therapeutic effect. Evidence from adeno-associated virus gene transfer, hematopoietic stem and progenitor cell gene therapy, retinal treatment, skeletal-muscle expression, and other somatic-cell platforms indicates that durability depends on vector fate, transcriptional competence, immune pressure, cell turnover, lineage contribution, tissue renewal, disease progression, and the choice and timing of longitudinal endpoints. The framework therefore treats durability as a multidimensional longitudinal property rather than a single binary state. A therapy can remain molecularly detectable while losing clinically relevant output, or retain functional benefit despite changes in one molecular proxy. Durable therapeutic function is most defensibly inferred when the biological layer being measured, the tissue and cellular substrate, the observation interval, and plausible alternative explanations are stated explicitly. This separation provides a basis for interpreting longitudinal gene-therapy outcomes without equating persistence of a component with persistence of benefit.
