UIMC1 (ubiquitin interaction motif containing 1), also known as RAP80, is a ubiquitin-binding protein that plays a critical role in DNA damage response and repair. Primary function: UIMC1 specifically recognizes Lys-63-linked ubiquitinated histones H2A and H2AX at DNA double-strand break (DSB) sites, serving as a key component of the BRCA1-A complex 1. Mechanism: Upon DNA damage, DOT1L-mediated methylation of UIMC1 enhances its binding to ubiquitinated H2A, which is essential for recruiting the BRCA1-BARD1 heterodimer to DSBs 1. Recent evidence demonstrates that UIMC1 undergoes liquid-liquid phase separation at DSBs in an intrinsically disordered region-dependent manner, with Lys-63-linked polyubiquitin chains strongly promoting this condensation to facilitate BRCA1 recruitment 2. Disease relevance: UIMC1 is implicated in neurodevelopmental disorders, with de novo mutations showing significant enrichment in autism and other NDDs 3. Clinical significance: SOX9 transcriptionally regulates UIMC1 expression as part of DNA damage repair pathways, and modulation of this regulation affects PARP inhibitor resistance in ovarian cancer 4. UIMC1 expression has also been associated with laryngeal squamous cell carcinoma progression and osteoarthritis diagnostics 5, 6.