Galactocerebrosidase (GALC) is the lysosomal enzyme deficient in human and 
certain animal species with globoid cell leukodystrophy (GLD) or Krabbe disease. 
It catalyzes the hydrolysis of specific galactolipids including 
galactosylceramide and psychosine. The GALC protein is found in very low amounts 
in all tissues, which delayed its purification and the subsequent cloning of its 
cDNA and gene. We previously published the exon-intron organization of the human 
gene, but did not functionally analyze the 5' flanking region. We now provide a 
description of this GC-rich region which includes one potential YY1 element and 
one potential SP1 binding site. There are 13 GGC trinucleotides within the first 
150 bp preceding the initiation codon. The 5' end of intron 1 contains six 
potential Sp1 binding sites, one AP1 binding site, and eight AP2 binding sites. 
A construct containing nucleotides -176 to -24 had the strongest promoter 
activity using a vector containing the chloramphenicol acetyltransferase 
reporter gene. We also provide evidence for the presence of inhibitory sequences 
located immediately upstream of the promoter region, and within the first 234 
nucleotides of intron 1. These elements together with a suboptimal nucleotide at 
position +4 may explain the low level of GALC protein in all cell types.