The article discusses the intricate relationship between cell signaling and endocytic membrane trafficking, highlighting how these processes are interconnected in animal cells. It emphasizes that endocytosis regulates receptor signaling, including from receptor tyrosine kinases (RTKs) and G protein-coupled receptors (GPCRs), while signaling also influences the endocytic pathway. The review covers mechanisms of receptor endocytosis, such as clathrin-dependent endocytosis (CDE) and clathrin-independent endocytosis (CIE), and the role of adaptor proteins like AP2 and β-arrestins. It also explores the importance of ubiquitylation in receptor endocytosis and post-endocytic receptor trafficking, including recycling and degradation pathways. The article further delves into how endocytosis attenuates cell signaling by reducing the number of receptors available for activation and separating receptors from substrates. It discusses sustained signaling in endosomes, particularly in RTKs and GPCRs, and the role of endosomes in specific signaling processes like TGFβ, GPCR, RTK, Notch, and tumor necrosis factor signaling. The review also examines how signaling influences endocytosis, including regulation of clathrin-mediated endocytosis (CDE) and endosomal sorting. Finally, it concludes by emphasizing the importance of integrating signaling and endocytosis into a single molecular network and the need for further research to understand their crosstalk in vivo.The article discusses the intricate relationship between cell signaling and endocytic membrane trafficking, highlighting how these processes are interconnected in animal cells. It emphasizes that endocytosis regulates receptor signaling, including from receptor tyrosine kinases (RTKs) and G protein-coupled receptors (GPCRs), while signaling also influences the endocytic pathway. The review covers mechanisms of receptor endocytosis, such as clathrin-dependent endocytosis (CDE) and clathrin-independent endocytosis (CIE), and the role of adaptor proteins like AP2 and β-arrestins. It also explores the importance of ubiquitylation in receptor endocytosis and post-endocytic receptor trafficking, including recycling and degradation pathways. The article further delves into how endocytosis attenuates cell signaling by reducing the number of receptors available for activation and separating receptors from substrates. It discusses sustained signaling in endosomes, particularly in RTKs and GPCRs, and the role of endosomes in specific signaling processes like TGFβ, GPCR, RTK, Notch, and tumor necrosis factor signaling. The review also examines how signaling influences endocytosis, including regulation of clathrin-mediated endocytosis (CDE) and endosomal sorting. Finally, it concludes by emphasizing the importance of integrating signaling and endocytosis into a single molecular network and the need for further research to understand their crosstalk in vivo.