AP2B1 (adaptor protein complex 2 subunit beta 1) is a core component of the AP-2 complex that mediates clathrin-dependent endocytosis. This adaptor complex functions as a crucial link between clathrin lattices and cellular membranes, facilitating cargo selection and clathrin-coated vesicle formation for receptor-mediated endocytosis 1. AP2B1 recognizes specific endocytosis signal motifs within transmembrane cargo cytoplasmic tails and serves as a scaffolding platform through its C-terminal appendage domain for clathrin-associated sorting proteins. AP2B1 plays significant roles in viral entry and neurodegeneration. During influenza A virus internalization, AP2B1 functions downstream of multiple signaling cascades: the FFAR2-β-arrestin1 pathway 2 and the SLC35B4-AGRN-mediated pathway 1, both promoting efficient viral endocytosis. Additionally, AP2B1 participates in synaptic vesicle recycling and long-term potentiation mechanisms. Clinically, AP2B1 demonstrates disease relevance in Alzheimer's disease, where elevated cerebrospinal fluid AP2B1 levels correlate with reduced synaptic density measured by [11C]UCB-J PET imaging 3, suggesting its involvement in synaptic pathology. CSF AP2B1 levels also differ between neurodegenerative diseases, being altered in Parkinson's disease relative to controls 4. Furthermore, AP2B1 expression is upregulated in breast cancer and associates with survival rates 5, and its expression is regulated by oncogenic ZHX2-HIF1α signaling in triple-negative breast cancer 6. AP2B1 also participates in Wnt16-regulated chondrocyte differentiation through the PCP/JNK pathway 7.