Mulibrey nanism is a rare growth disorder of prenatal onset caused by mutations 
in the TRIM37 gene, which encodes a RING-B-box-coiled-coil protein. The 
pathogenetic mechanisms of mulibrey nanism are unknown. We have used transiently 
transfected cells and antibodies raised against the predicted TRIM37 protein to 
characterize the TRIM37 gene product and to determine its intracellular 
localization. We show that the human TRIM37 cDNA encodes a peroxisomal protein 
with an apparent molecular weight of 130 kD. Peroxisomal localization is 
compromised in mutant protein representing the major Finnish TRIM37 mutation but 
is retained in the protein representing the minor Finnish mutation. 
Colocalization of endogenous TRIM37 with peroxisomal markers was observed by 
double immunofluorescence staining in HepG2 and human intestinal smooth muscle 
cell lines. In human tissue sections, TRIM37 shows a granular cytoplasmic 
pattern. Endogenous TRIM37 is not imported into peroxisomes in peroxin 1 
(PEX1(-/-)) and peroxin 5 (PEX5(-/-)) mutant fibroblasts but is imported 
normally in peroxin 7 (PEX7(-/-)) deficient fibroblasts, giving further evidence 
for a peroxisomal localization of TRIM37. Fibroblasts derived from patients with 
mulibrey nanism lack C-terminal TRIM37 immunoreactivity but stain normally for 
both peroxisomal matrix and membrane markers, suggesting apparently normal 
peroxisome biogenesis in patient fibroblasts. Taken together, this molecular 
evidence unequivocally indicates that TRIM37 is located in the peroxisomes, and 
Mulibrey nanism thus can be classified as a new peroxisomal disorder.