Within the decade following the demonstration that mutations in the RPS19 gene 
can lead to Diamond-Blackfan anemia (DBA), this disease has become a paradigm 
for an emerging group of pathologies linked to defects in ribosome biogenesis. 
DBA patients exhibit abnormal pre-rRNA maturation patterns and the majority bear 
mutations in one of several ribosomal protein genes that encode structural 
components of the ribosome essential for the correct assembly of the ribosomal 
subunits. Extensive study of the most frequently mutated gene, RPS19, has shown 
that mutations prevent the assembly of the ribosomal protein into forming 
pre-ribosomal particles. This defect in ribosome production triggers nucleolar 
stress pathways, the activation of which appears to be central to 
pathophysiological mechanisms. Why mutations in ribosomal protein genes so 
strongly and specifically affect erythropoiesis in DBA remains a challenging 
question, especially given the fact that defects in genes encoding nonstructural 
ribosome biogenesis factors have been shown to cause diseases other than DBA. A 
major problem in understanding the pathophysiological mechanisms in DBA remains 
the lack of a suitable animal model. Despite this, considerable strides have 
been made over that past few years demonstrating that several factors involved 
in the synthesis of ribosomes are targets of disease-causing mutations.