The human Transducin-like Enhancer of Split (TLE) and mouse homologue, Groucho 
gene-related protein (GRG), represent a family of conserved non-DNA binding 
transcriptional modulatory proteins divided into two subgroups based upon size. 
The long TLE/GRGs consist of four pentadomain proteins that are dedicated 
co-repressors for multiple transcription factors (TF). The second TLE/GRG 
subgroup is composed of the Amino-terminal Enhancer of Split (AES) in humans and 
its mouse homolog GRG5 (AES/GRG5). In contrast to the dedicated co-repressor 
function of long TLE/GRGs, AES/GRG5 can both positively or negatively modulate 
various TF as well as non-TF proteins in a long TLE/GRG-dependent or 
-independent manner. Therefore, AES/GRG5 is a functionally dynamic protein that 
is not exclusively defined by its role as a long TLE/GRG antagonist. AES/GRG5 
may function in various developmental and pathological processes but the 
functional characteristics of endogenous AES/GRG5 in a physiologically relevant 
context remains to be determined.