Arrestin domain-containing protein 1 (ARRDC1)

**Arrestin domain-containing protein 1 (ARRDC1)** is an adaptor protein belonging to the alpha-arrestin family, characterized by an N-terminal arrestin domain and C-terminal PPXY and PSAP motifs[1][4]. ARRDC1 is primarily involved in the regulation of plasma-membrane derived extracellular vesicle (EV) biogenesis, specifically the formation of *ARRDC1-mediated microvesicles* (ARMMs), which are key for intercellular communication[1][5]. It interacts with components of the *endosomal sorting complexes required for transport* (ESCRT) machinery, especially TSG101, through its PSAP motif, recruiting these factors from endosomes to the plasma membrane and enabling the budding and release of microvesicles[1][5]. ARRDC1 also recruits E3 ubiquitin ligases such as WWP2 and participates in protein ubiquitination processes[3][4]. Functionally, it acts as a negative regulator of Notch signaling by promoting NOTCH1 ubiquitination and degradation[2][3]. There is evidence supporting a role in cancer, particularly hepatocellular carcinoma, where ARRDC1-driven vesicle release remodels the tumor microenvironment[3]. Despite involvement in disease processes, ARRDC1 is not a therapeutic target in the conventional sense (receptor, enzyme, transporter, etc.), and no drugs are reported to bind or inhibit it directly[2][3]. **Note:** ARRDC1 is sometimes referred to as "Alpha-arrestin 1," and its gene is listed in databases such as UniProt (Q8N5I2) and HGNC (28633)[2][3]. It is a protein-coding gene with important roles at the plasma membrane and in the extracellular space but is not classified as a traditional druggable target[2][3][6].

Other names

ARRDC1Alpha-arrestin 1alpha-arrestin 1MGC40555

Not applicable; there are no known drugs targeting ARRDC1 directly. ARRDC1 acts as an adaptor protein affecting ubiquitination and vesicle release pathways but is not a direct receptor or enzyme target.