Anatomy journal of Africa, 5(1): 618-630Cathepsins, are members of the papain superfamily of mammalian lysosomal cysteine proteases. Among others there are two prominent members with broad substrate specificity, these are cathepsin B and cathepsin L that are known to be involved in the process of intra- and extra-cellular protein degradation and turnover. However, the in vivo targets of cathepsin L in nervous tissues are yet to be identified. We examined by immunofluorescence studies the distribution pattern of cathepsin L protein and determine the specific cell types synthesizing the enzyme in the brain of African giant rats (Cricetomys gambianus). Results showed that Cathepsin L protein was localized in various brain regions of the giant rats. In the telencephalon, immunoreactivity was identified in cerebral cortex and subcortical structures, hippocampus, amygdala and basal ganglia. Within the diencephalon high density of positive signals was observed in mediodorsal and lateral posterior thalamic nuclei and medial habenular nucleus. In the mesencephalon, cathepsin L was detected in the substantia nigra and cerebral peduncles. Strong labeling in the hypothalamus was present in the anterior commissure and median eminence while in the cerebellum cathepsin L was observed in the deep white matter, granule cell layer, stellate, and basket cells of cerebellar cortex and in the Purkinje neurons. The distribution pattern and functional implications of cathespin L in relation to spatial memory establishment, learning coordination and disease mechanisms is discussed.