Arrb1, also known as arrestin beta 1, is a multifunctional protein. It acts as a molecular scaffold and is involved in regulating signaling downstream of G protein-coupled receptors (GPCRs) [6]. It participates in various biological processes such as autophagy, lipid metabolism, and metabolic reprogramming, which are crucial for maintaining normal cellular functions and organismal homeostasis.

In several disease models, Arrb1 has shown distinct roles. In hepatocellular carcinoma, Arrb1 deficiency suppressed HBx-induced hepatocellular carcinogenesis in mouse models. It was found that HBx upregulates Arrb1, and Arrb1-mediated autophagy drives the G1/S cell cycle, indicating its role in HBV-related HCC [1]. In non-alcoholic steatohepatitis (NASH), Arrb1-knockout mice fed a high-fat or methionine/choline-deficient diet showed accelerated steatohepatitis development. Arrb1 interacts with GDF15 to facilitate its maturation, and its deficiency leads to lipid accumulation [2]. In acetaminophen-induced liver injury, systemic Arrb1-KO mice were more susceptible to hepatotoxicity, with increased endoplasmic reticulum (ER) stress and apoptosis [3]. In gallbladder cancer, knockdown of Arrb1 in in vitro and in vivo experiments revealed that it enhanced cell proliferation, migration, and invasion through the TNF/TAK1/MAPK axis [4]. In intervertebral disc degeneration, Arrb1 knockdown in rat nucleus pulposus cells aggravated extracellular matrix degradation, apoptosis, and autophagic flux impairment, while overexpression reversed these effects [5]. In bladder cancer, depletion of Arrb1 in cancer stem-like cells decreased glycolytic rate and induced metabolic reprogramming towards oxidative phosphorylation [6]. In T-cell acute lymphoblastic leukemia, exogenous expression of Arrb1 inhibited T-ALL proliferation and improved the survival of xenograft animals [7].

In conclusion, Arrb1 is involved in diverse biological functions, and its dysregulation is associated with multiple diseases including liver cancers, NASH, drug-induced liver injury, gallbladder cancer, intervertebral disc degeneration, bladder cancer, and T-cell acute lymphoblastic leukemia. Gene knockout mouse models have been instrumental in uncovering these disease-related roles of Arrb1, providing insights into potential therapeutic targets for these diseases.