ADRM1 (adhesion-regulating molecule 1) is a ubiquitin receptor component of the 26S proteasome that recognizes and binds polyubiquitinated protein substrates destined for degradation. Its N-terminal pleckstrin-like receptor (Pru) domain binds ubiquitin, while its C-terminal DEUBAD domain activates the deubiquitinases UCH37 and PSMD14, which remove ubiquitin chains from substrates before proteasomal degradation 1. By coordinating substrate recognition and deubiquitination, ADRM1 maintains protein homeostasis and participates in cell cycle progression, apoptosis, and DNA damage repair. Beyond proteasomal function, ADRM1 regulates cell adhesion, cytoskeletal dynamics, bone metabolism, and immune responses by interacting with proteins including Phg2, HDAC8, and PADI4 1. ADRM1 is significantly overexpressed across multiple malignancies—including colorectal, ovarian, gastric, hepatic, breast, and lung cancers, as well as multiple myeloma and kidney renal clear cell carcinoma—where elevated expression correlates with poor prognosis, tumor proliferation, metastasis, and therapeutic resistance 2345. In hepatocellular carcinoma, a spliced ADRM1 variant (ADRM1-ΔEx9) selectively degrades the tumor suppressor FBXW7 and confers sensitivity to olaparib 6. Conversely, in osteoarthritis, ADRM1 expression is protective, reducing cartilage degradation via ALK5 stabilization 7. Small-molecule ADRM1 inhibitors including RA190 and Up284 show anti-tumor efficacy across diverse cancer cell types, with Up284 demonstrating tolerability and activity in mouse xenograft and syngeneic models 89.