NMD3 is a nucleocytoplasmic adaptor protein that mediates nuclear export of the 60S ribosomal subunit in an XPO1/CRM1-dependent manner 1. NMD3 contains a leucine-rich nuclear export signal recognized by CRM1 and a complex nuclear localization signal required for nucleolar accumulation 1. The protein binds to maturing 60S pre-export particles at late maturation stages and acts as a functional adaptor coupling 60S subunit recognition to CRM1-mediated export 1. NMD3 nucleolar localization is independent of CRM1 activity, suggesting it provides nucleolar tethering of the export machinery 2. Beyond export, NMD3 participates in coordinating rRNA synthesis rates with processing efficiency; NMD3 depletion reduces pre-47S rRNA synthesis without directly affecting transcription 2. The protein also interacts genetically with ribosomal protein L10 in translational control 3. Clinically, NMD3 variants show disease associations: the rs34016896 polymorphism correlates with cognitive impairment in Parkinson's disease patients 4 and influences PD symptomatology phenotypes 5. NMD3 is a therapeutic target; the marine compound portimine A selectively induces cancer cell apoptosis through NMD3 inhibition 6. Selinexor sensitivity in multiple myeloma involves NMD3-mediated nuclear export regulation 7.