Diamond-Blackfan anemia (DBA) is a rare congenital disease affecting erythroid 
precursor differentiation. DBA is emerging as a paradigm for a new class of 
pathologies potentially linked to disorders in ribosome biogenesis. Three genes 
encoding ribosomal proteins have been associated to DBA: after RPS19, mutations 
in genes RPS24 and RPS17 were recently identified in a fraction of the patients. 
Here, we show that cells from patients carrying mutations in RPS24 have 
defective pre-rRNA maturation, as in the case of RPS19 mutations. However, in 
contrast to RPS19 involvement in the maturation of the internal transcribed 
spacer 1, RPS24 is required for processing of the 5' external transcribed 
spacer. Remarkably, epistasis experiments with small interfering RNAs indicate 
that the functions of RPS19 and RPS24 in pre-rRNA processing are connected. 
Resolution of the crystal structure of RPS24e from the archeon Pyroccocus abyssi 
reveals domains of RPS24 potentially involved in interactions with 
pre-ribosomes. Based on these data, we discuss the impact of RPS24 mutations and 
speculate that RPS19 and RPS24 cooperate at a particular stage of ribosome 
biogenesis connected to a cell cycle checkpoint, thus affecting differentiation 
of erythroid precursors as well as developmental processes.