EPS15（Epidermal Growth Factor Receptor Pathway Substrate 15）是一种参与细胞信号转导和内吞作用的衔接蛋白，主要通过与表皮生长因子受体（EGFR）等受体酪氨酸激酶相互作用来调控细胞增殖、分化和迁移。EPS15的表达产物是一种多功能蛋白，含有多个蛋白相互作用结构域，如EH结构域（Eps15 homology domain）和 coiled-coil 结构域，使其能够与多种信号分子和膜运输相关蛋白结合。EPS15在网格蛋白介导的内吞作用（CME）中发挥关键作用，帮助招募网格蛋白和其他内吞相关蛋白到细胞膜上，从而促进受体的内化和下游信号传导。EPS15的突变或异常表达可能破坏内吞过程，导致受体信号失调，进而影响细胞生长和存活。研究发现，EPS15的突变或缺失可能增加癌症风险，特别是在乳腺癌和肺癌中，EPS15的表达异常与肿瘤发生和转移相关。此外，EPS15还与神经退行性疾病有关，如阿尔茨海默病，因其参与突触囊泡的循环和神经递质的释放。当EPS15过表达时，可能增强受体介导的信号传导，促进细胞过度增殖，甚至导致肿瘤发生；而降低EPS15表达则可能抑制内吞作用，影响受体的降解和信号传递，导致细胞功能紊乱。EPS15属于EPS15基因家族，该家族还包括EPS15L1（EPS15-like 1），两者在结构和功能上高度相似，均参与内吞和信号转导调控。EPS15家族的共性在于它们都含有EH结构域和 coiled-coil 区域，能够与多种蛋白相互作用，协调细胞内吞和信号传导过程。这一家族在维持细胞稳态和响应外界信号中发挥重要作用，其功能异常可能导致多种疾病的发生。

这个基因编码的蛋白质，它是表皮生长因子受体途径的一部分。该蛋白质存在于clatherin涂覆凹坑和参与的EGF受体介导的内吞作用。值得注意的是，这种基因重排与急性髓细胞性白血病的HRX / ALL / MLL基因。在多个转录剪接变异体结果不同编码的亚型。 [由RefSeq的，2009年5月提供]

EPS15, also known as Epidermal Growth Factor Receptor Pathway Substrate 15, is a critical scaffolding protein that orchestrates cell signaling and endocytosis by physically linking receptor tyrosine kinases, such as the epidermal growth factor receptor (EGFR), to the cellular endocytic machinery. As a member of the EPS15 family, which includes the closely related EPS15L1, this protein features conserved structural motifs, including an Eps15 homology (EH) domain and a coiled-coil region, that enable it to interact with a diverse array of signaling molecules and membrane transport components. Its primary biological role is to facilitate clathrin-mediated endocytosis (CME) by recruiting clathrin and other endocytic adaptor proteins to the plasma membrane, thereby promoting the internalization of receptors and the subsequent modulation of downstream proliferative, differentiation, and migratory pathways. The precise regulation of EPS15 levels is essential for maintaining cellular homeostasis; overexpression can hyperactivate receptor-mediated signaling, driving excessive cell proliferation and contributing to tumorigenesis, particularly in breast and lung cancers, while its loss or mutation impairs receptor degradation and signal transduction, leading to cellular dysfunction. Beyond its role in oncogenesis, EPS15 is implicated in neurodegenerative conditions such as Alzheimer’s disease, where it supports synaptic vesicle recycling and neurotransmitter release, highlighting its broad impact on cellular physiology and its potential as a therapeutic target in both cancer and neurological disorders.

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