In normal bone marrow erythroid progenitors (left panel), HEATR3 acts as a shuttling factor that imports ribosomal protein uL18 from the cytoplasm to the nucleus. There, it associates with uL5 and the 5S ribosomal RNA (rRNA) to form the 5S ribonucleoprotein (RNP) complex, which is incorporated with maturing large ribosomal subunits to form the central protuberance. Intact ribosome biogenesis is a prerequisite for erythroid progenitor proliferation and differentiation to red blood cells. Biallelic HEATR3 variants destabilize the HEATR3 protein, reducing nuclear uL18 (right panel). HEATR3 variants cause pre-RNA processing defects, reduced 60S ribosomal subunits, and failure of erythropoiesis, presenting clinically as anemia. Professional illustration by Somersault18:24.