The interaction of heat shock proteins (HSP) with cellular membranes has been an enigmatic process, initially observed by morphological studies, inferred during the purification of HSP70s, and confirmed after the detection of these proteins on the surface of cancer cells and their insertion into artificial lipid bilayers. Today, the association of several HSP with lipid membranes is well established. However, the mechanisms for membrane insertion have been elusive. There is conclusive evidence indicating that HSP70s have a great selectivity for negatively charged phospholipids, whereas other HSP have a broader spectrum of lipid specificity. HSP70 also oligomerizes upon membrane insertion, forming ion conductance channels. The functional role of HSP70 lipid interactions appears related to membrane stabilization that may play a role during cell membrane biogenesis. They could also play a role as membrane chaperones as well as during endocytosis, microautophagy, and signal transduction. Moreover, HSP membrane association is a key component in the extracellular export of these proteins. The presence of HSP70 on the surface of cancer cells and its interaction with lysosome membranes have been envisioned as potential therapeutic targets. Thus, the biology and function of HSP membrane association are reaching a new level of excitement. This review is an attempt to preserve the recollection of the pioneering contributions of many investigators that have participated in this endeavor.

热休克蛋白 (HSP) 与细胞膜的相互作用一直是一个神秘的过程，最初通过形态学研究观察到，在 HSP70 纯化过程中推断，并在癌细胞表面检测到这些蛋白质并将其插入人工脂双层。今天，几种 HSP 与脂质膜的关联已经很好地建立起来。然而，膜插入的机制一直难以捉摸。有确凿的证据表明 HSP70 对带负电荷的磷脂具有很强的选择性，而其他 HSP 具有更广泛的脂质特异性。HSP70 也会在膜插入时寡聚化，形成离子传导通道。HSP70 脂质相互作用的功能作用似乎与可能在细胞膜生物发生过程中发挥作用的膜稳定性有关。它们还可以作为膜伴侣以及在内吞作用、微自噬和信号转导过程中发挥作用。此外，HSP 膜结合是这些蛋白质细胞外输出的关键组成部分。HSP70 在癌细胞表面的存在及其与溶酶体膜的相互作用已被设想为潜在的治疗靶点。因此，HSP 膜结合的生物学和功能达到了令人兴奋的新水平。这篇综述试图保留对参与这项工作的许多研究人员的开创性贡献的回忆。它们还可以作为膜伴侣以及在内吞作用、微自噬和信号转导过程中发挥作用。此外，HSP 膜结合是这些蛋白质细胞外输出的关键组成部分。HSP70 在癌细胞表面的存在及其与溶酶体膜的相互作用已被设想为潜在的治疗靶点。因此，HSP 膜结合的生物学和功能达到了令人兴奋的新水平。这篇综述试图保留对参与这项工作的许多研究人员的开创性贡献的回忆。它们还可以作为膜伴侣以及在内吞作用、微自噬和信号转导过程中发挥作用。此外，HSP 膜结合是这些蛋白质细胞外输出的关键组成部分。HSP70 在癌细胞表面的存在及其与溶酶体膜的相互作用已被设想为潜在的治疗靶点。因此，HSP 膜结合的生物学和功能达到了令人兴奋的新水平。这篇综述试图保留对参与这项工作的许多研究人员的开创性贡献的回忆。HSP70 在癌细胞表面的存在及其与溶酶体膜的相互作用已被设想为潜在的治疗靶点。因此，HSP 膜结合的生物学和功能达到了令人兴奋的新水平。这篇综述试图保留对参与这项工作的许多研究人员的开创性贡献的回忆。HSP70 在癌细胞表面的存在及其与溶酶体膜的相互作用已被设想为潜在的治疗靶点。因此，HSP 膜结合的生物学和功能达到了令人兴奋的新水平。这篇综述试图保留对参与这项工作的许多研究人员的开创性贡献的回忆。