Fragile X-associated Conditions (FXaCs), including Fragile X Syndrome (FXS), fragile X-associated tremor/ataxia syndrome (FXTAS), fragile X-associated primary ovarian insufficiency (FXPOI), and fragile X-associated neuropsychiatric disorders (FXAND), are a heterogeneous group of disorders arising from alterations in the size and epigenetic state of a polymorphic CGG repeat within FMR1. Described as the first repeat expansion disorder over 30 years ago, FMR1 CGG repeat expansions are both an important cause of neurological, reproductive, and neurodevelopmental disease. Over more than three decades of research, significant advancements have been made in understanding the function of the FMR1 gene and characterizing the underlying disease mechanisms using mouse, rat, and fruit fly models and, more recently, human brain organoids. Early on, our group identified mRNA ligands of FMRP and demonstrated the biochemical and genetic interaction between FMRP and the microRNA pathway. Using Drosophila as a model system, his lab showed that the long repeat tracks in FMR1 mRNA drove pathology in FXTAS. His program continues to lead the field in discovering the mechanisms associated with FXTAS and FXS. More recently, he has focused on developing a human brain organoid model for FXS and identifying the genetic modifiers of both FXS and FXTAS.