Short tandem repeats (STRs), a frequently overlooked yet significant component of the human genome, play a vital role in gene expression and regulation. These repetitive sequences constitute more than a third of our DNA. Historically, research has predominantly focused on the pathological consequences of STR expansions in various syndromic human diseases. However, emerging evidence indicates that STRs hold crucial native functions in gene regulation. Interestingly, the majority of STRs in the genome do not reside within genes. The relationship between these intergenic STRs and disease is less understood. While the STR tracts associated with known diseases are typically located within gene bodies – including exons, introns, or untranslated regions – pathogenic-length expansions of these disease-associated STRs are linked to broader biological disruptions. These include significant histone modifications, DNA methylation, and genome architecture alterations. In particular, we are interested in GC-rich polymorphic repeats, particularly CGG repeats. Besides Fragile X-related disorders, we have contributed to the discovery of additional disorders that could be caused by CGG repeat expansion.