RITA1 (RBPJ interacting and tubulin associated 1) is a tubulin-binding protein that functions as a negative regulator of Notch signaling. However, recent evidence reveals a complex and context-dependent role in disease. In bladder cancer, RITA1 is aberrantly overexpressed and promotes tumor growth by recruiting TRIM25 to ubiquitinate and degrade RBPJ, leading to suppression of Notch1 downstream targets 1. This contrasts with its canonical function as a Notch pathway inhibitor. RITA1 has emerged as a genetic risk factor in multiple neurodegenerative conditions: genome-wide association studies identified RITA1 as a novel candidate causal gene for Lewy body dementia through differential expression in brain tissues and neurons 2, and as a risk gene for lung cancer through non-coding regulatory mechanisms 3. Additionally, RITA1 mutations have been detected in refractory testicular germ cell tumors 4. Brain region-specific DNA methylation changes at RITA1 loci (cg11558705) have been associated with Alzheimer's disease risk through Mendelian randomization analysis 5. These findings suggest RITA1 plays multifaceted roles in cancer progression and neurodegeneration, with potential as a therapeutic target in bladder cancer and biomarker in neurodegenerative diseases.