Stromal interaction molecules (STIMs), including STIM1 and STIM2, are single-pass transmembrane proteins that are located predominantly in the endoplasmic reticulum (ER). They serve as calcium ion (Ca²⁺) sensors within the ER. In the central nervous system (CNS), they are involved mainly in Orai-mediated store-operated Ca²⁺ entry (SOCE). The key molecular components of the SOCE pathway are well-characterized, but the molecular mechanisms that underlie the regulation of this pathway need further investigation. Numerous intracellular target proteins that are located in the plasma membrane, ER, cytoskeleton, and cytoplasm have been reported to play essential roles in concert with STIMs, such as conformational changes in STIMs, their translocation, the stabilization of their interactions with Orai, and the activation of other channels. The present review focuses on numerous regulators, such as Homer, SOCE-associated regulatory factor (SARAF), septin, synaptopodin, golli proteins, partner of STIM1 (POST), and transcription factors and proteasome inhibitors that regulate STIM-Orai interactions in the CNS. Further we describe novel roles of STIMs in mediating Ca²⁺ influx via other than Orai pathways, including TRPC channels, VGCCs, AMPA and NMDA receptors, and group I metabotropic glutamate receptors. This review also summarizes recent findings on additional molecular targets of STIM proteins including SERCA, IP₃Rs, end-binding proteins (EB), presenilin, and CaMKII. Dysregulation of the SOCE-associated toolkit, including STIMs, contributes to the development of neurodegenerative disorders (e.g., Alzheimer's disease, Parkinson's disease, and Huntington's disease), traumatic brain injury, epilepsy, and stroke. Emerging evidence points to the role of STIM proteins and several of their molecular effectors and regulators in neuronal and glial physiology and pathology, suggesting their potential application for future therapeutic strategies.

基质相互作用分子（STIM），包括STIM1和STIM2，是单程跨膜蛋白，主要位于内质网（ER）中。它们充当ER中的钙离子（Ca ²⁺）传感器。在中枢神经系统（CNS）中，它们主要参与Orai介导的存储操纵性Ca ²⁺条目（SOCE）。SOCE途径的关键分子成分已被很好地表征，但是作为该途径调控基础的分子机制需要进一步研究。据报道，位于质膜，内质网，细胞骨架和细胞质中的许多细胞内靶蛋白与STIM协同发挥重要作用，例如STIM的构象变化，易位，与Orai相互作用的稳定化以及激活其他渠道。本文综述了许多调节因子，如荷马，SOCE相关调节因子（SARAF），Septin，突触足蛋白，golli蛋白，STIM1的伴侣（POST）以及调节CNS中STIM-Orai相互作用的转录因子和蛋白酶体抑制剂。 。此外，我们描述了STIM在介导Ca中的新作用。^2种以上通过Orai途径以外的途径流入，包括TRPC通道，VGCC，AMPA和NMDA受体以及I组代谢型谷氨酸受体。这篇综述还总结了关于STIM蛋白其他分子靶标的最新发现，包括SERCA，IP ₃ Rs，末端结合蛋白（EB），早老素和CaMKII。与SOCE相关的工具包（包括STIM）的失调会导致神经退行性疾病（例如阿尔茨海默氏病，帕金森氏病和亨廷顿氏病），脑外伤，癫痫和中风的发展。新兴证据表明STIM蛋白及其分子效应物和调节物在神经元和神经胶质的生理和病理中的作用，表明它们在未来治疗策略中的潜在应用。