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Simple Summary: Basement membranes (BMs) are thin sheets of connective tissue that form boundary layers in the organs of most animal bodies. There is increasing interest in how changes in the strength and stiffness of BMs contribute to the normal processes by which fertilized eggs become mature adults and the abnormal processes associated with disease, such as the spread of cancerous tumors. The spread of cancer can be helped by the weakening and disruption of BMs, which is thought to result mainly from BM components being broken down by specific enzymes, although other factors may be involved. Brittlestars are marine invertebrate animals related to starfish and sea urchins. The BMs of their muscles act as tendons that link the muscles to the skeleton. Brittlestars are able to jettison their arms when they are attacked by predators. Such arm loss depends partly on the ability of muscles to detach from the skeleton due to the sudden weakening of their tendons. This contribution provides an overview of current knowledge of the structure and mechanical behavior of BMs in non-echinoderm animals and of brittlestar tendons and discusses the possible usefulness of brittlestar tendons as a model for understanding mechanisms of BM weakening in normal and disease-related processes. Basement membranes (BMs) are thin layers of extracellular matrix that separate epithelia, endothelia, muscle cells, and nerve cells from adjacent interstitial connective tissue. BMs are ubiquitous in almost all multicellular animals, and their composition is highly conserved across the Metazoa. There is increasing interest in the mechanical functioning of BMs, including the involvement of altered BM stiffness in development and pathology, particularly cancer metastasis, which can be facilitated by BM destabilization. Such BM weakening has been assumed to occur primarily through enzymatic degradation by matrix metalloproteinases. However, emerging evidence indicates that non-enzymatic mechanisms may also contribute. In brittlestars (Echinodermata, Ophiuroidea), the tendons linking the musculature to the endoskeleton consist of extensions of muscle cell BMs. During the process of brittlestar autotomy, in which arms are detached for the purpose of self-defense, muscles break away from the endoskeleton as a consequence of the rapid destabilization and rupture of their BM-derived tendons. This contribution provides a broad overview of current knowledge of the structural organization and biomechanics of non-echinoderm BMs, compares this with the equivalent information on brittlestar tendons, and discusses the possible relationship between the weakening phenomena exhibited by BMs and brittlestar tendons, and the potential translational value of the latter as a model system of BM destabilization. [ABSTRACT FROM AUTHOR]