ADRM1 (adhesion-regulating molecule 1), also known as RPN13, is a multifunctional 26S proteasome ubiquitin receptor that serves as a key component of the ubiquitin-proteasome system 1. Its N-terminal Pru domain recognizes ubiquitinated substrates for proteasomal degradation, while its C-terminal DEUBAD domain activates the deubiquitinating enzyme UCH37 1. ADRM1 facilitates substrate recognition and coordinates deubiquitination within the 26S proteasome, thereby regulating protein homeostasis and participating in cell cycle progression, apoptosis, and DNA damage repair 1. Beyond proteasomal function, ADRM1 modulates cytoskeletal remodeling, cell adhesion, and immune regulation through interactions with proteins including Phg2, HDAC8, and PADI4 1. Clinically, ADRM1 is significantly upregulated across multiple malignancies including hepatocellular carcinoma, gastric cancer, lung adenocarcinoma, ovarian cancer, kidney renal clear cell carcinoma, and bladder cancer, where it promotes tumor proliferation, migration, metastasis, and therapeutic resistance [PMID:39788431; 2; 3; 4; 5; 67]. Disease-specific mechanisms include selective degradation of tumor suppressors (FBXW7 in HCC) and modulation of immune checkpoints and immune cell infiltration [PMID:39788431; 5; 67]. Notably, a spliced ADRM1 variant (ADRM1-ΔEx9) in HCC exhibits enhanced oncogenicity through altered deubiquitinase specificity 7. Conversely, in osteoarthritis, ADRM1 loss accelerates cartilage degeneration, highlighting protective functions in non-malignant contexts 8. Small-molecule ADRM1 inhibitors like RA190 show promise as anti-tumor agents [PMID:28784174; 94].