β-Arrestins (ARRBs), the best known regulators of G protein-coupled receptor signaling, are versatile and multifunctional adapter proteins that regulate diverse cellular functions, including cell growth, apoptosis and immune responses. Phospho‑β‑arrestin 1 (Ser412) is a key phosphorylated isoform of β‑arrestin 1. Its Ser412 residue is mainly phosphorylated by ERK, governing GPCR desensitization, receptor internalization and downstream signal transduction. This modification regulates β‑arrestin 1 subcellular localization and scaffold function, participating in cell proliferation and insulin‑related ERK signaling desensitization as a vital negative feedback regulator. (PMID: 10347142, PMID: 15520010)