Endocytosis and signaling are closely linked in animal cells, with recent studies showing that endocytosis regulates receptor signaling and vice versa. This relationship is evident in various signaling pathways, including those involving receptor tyrosine kinases (RTKs) and G protein-coupled receptors (GPCRs). Endocytosis controls the number of receptors available for activation at the plasma membrane, and receptor activation often stimulates endocytosis. This bidirectional regulation forms a homeostatic loop to prevent excessive signaling. The mechanisms of receptor endocytosis involve clathrin-coated pits, and various adaptor proteins, such as AP2 and β-arrestins, facilitate this process. Ubiquitylation plays a key role in receptor endocytosis, with different ubiquitin chains serving distinct functions. Post-endocytic trafficking of signaling receptors involves sorting to recycling and degradation pathways, with endosomes serving as important signaling platforms. Endosomes can sustain signaling through the presence of specific proteins and lipid molecules, and endosomal signaling can occur in two forms: signaling that can take place in endosomes but also at the plasma membrane, and signaling that requires endocytosis. Continuous signaling in endosomes is observed in various systems, including RTKs and GPCRs, and endosomal sorting is regulated by various mechanisms, including ESCRT complexes. Signaling also influences endocytosis, with examples showing that signaling can regulate the formation and recycling of endocytic vesicles. The integration of signaling and endocytosis suggests that these processes are part of a single molecular network, with significant implications for cellular function and disease.Endocytosis and signaling are closely linked in animal cells, with recent studies showing that endocytosis regulates receptor signaling and vice versa. This relationship is evident in various signaling pathways, including those involving receptor tyrosine kinases (RTKs) and G protein-coupled receptors (GPCRs). Endocytosis controls the number of receptors available for activation at the plasma membrane, and receptor activation often stimulates endocytosis. This bidirectional regulation forms a homeostatic loop to prevent excessive signaling. The mechanisms of receptor endocytosis involve clathrin-coated pits, and various adaptor proteins, such as AP2 and β-arrestins, facilitate this process. Ubiquitylation plays a key role in receptor endocytosis, with different ubiquitin chains serving distinct functions. Post-endocytic trafficking of signaling receptors involves sorting to recycling and degradation pathways, with endosomes serving as important signaling platforms. Endosomes can sustain signaling through the presence of specific proteins and lipid molecules, and endosomal signaling can occur in two forms: signaling that can take place in endosomes but also at the plasma membrane, and signaling that requires endocytosis. Continuous signaling in endosomes is observed in various systems, including RTKs and GPCRs, and endosomal sorting is regulated by various mechanisms, including ESCRT complexes. Signaling also influences endocytosis, with examples showing that signaling can regulate the formation and recycling of endocytic vesicles. The integration of signaling and endocytosis suggests that these processes are part of a single molecular network, with significant implications for cellular function and disease.