Fragile X syndrome is caused by the absence of the fragile X mental retardation protein (FMRP). This study examines dendritic spines in the cerebral cortex of Fmr1 knockout mice, which lack FMRP. These mice exhibit longer, thinner, and more tortuous dendritic spines compared to wild-type mice, similar to those observed in humans with fragile X syndrome. Spine density along apical dendrites is also higher in knockout mice, suggesting impaired synaptic stabilization and pruning processes. Fragile X syndrome is the most common inherited form of intellectual disability after Down syndrome. It is an X-linked disorder with a prevalence of 1 in 2,000 in males. The FMR1 gene contains a trinucleotide repeat that is expanded in affected individuals, leading to hypermethylation of the promoter region and absence of FMRP. Previous studies linked immature dendritic spine morphology to some forms of intellectual disability. In fragile X patients, thin, elongated spines and small synaptic contacts are observed. Transgenic Fmr1 knockout mice were created, showing increased testicular size and impaired performance in the Morris water maze, similar to human symptoms. Using Golgi-Cox impregnation, the study found that knockout mice had longer and more tortuous spines, with increased spine density. These findings suggest that FMRP is essential for normal spine development and synaptic pruning. The study also shows that FMRP is synthesized locally at synapses in response to synaptic activity. FMRP contains RNA-binding domains and binds approximately 4% of fetal human brain mRNAs. Its function is not fully understood, but it is likely involved in synaptic maturation and stabilization. The results suggest that FMRP plays a critical role in the development of adult synaptic architecture. The study highlights the importance of FMRP in synaptic development and pruning, and suggests that Fmr1 knockout mice may serve as a model for fragile X syndrome. The findings support the idea that FMRP is essential for the development of synaptic structures in the brain.Fragile X syndrome is caused by the absence of the fragile X mental retardation protein (FMRP). This study examines dendritic spines in the cerebral cortex of Fmr1 knockout mice, which lack FMRP. These mice exhibit longer, thinner, and more tortuous dendritic spines compared to wild-type mice, similar to those observed in humans with fragile X syndrome. Spine density along apical dendrites is also higher in knockout mice, suggesting impaired synaptic stabilization and pruning processes. Fragile X syndrome is the most common inherited form of intellectual disability after Down syndrome. It is an X-linked disorder with a prevalence of 1 in 2,000 in males. The FMR1 gene contains a trinucleotide repeat that is expanded in affected individuals, leading to hypermethylation of the promoter region and absence of FMRP. Previous studies linked immature dendritic spine morphology to some forms of intellectual disability. In fragile X patients, thin, elongated spines and small synaptic contacts are observed. Transgenic Fmr1 knockout mice were created, showing increased testicular size and impaired performance in the Morris water maze, similar to human symptoms. Using Golgi-Cox impregnation, the study found that knockout mice had longer and more tortuous spines, with increased spine density. These findings suggest that FMRP is essential for normal spine development and synaptic pruning. The study also shows that FMRP is synthesized locally at synapses in response to synaptic activity. FMRP contains RNA-binding domains and binds approximately 4% of fetal human brain mRNAs. Its function is not fully understood, but it is likely involved in synaptic maturation and stabilization. The results suggest that FMRP plays a critical role in the development of adult synaptic architecture. The study highlights the importance of FMRP in synaptic development and pruning, and suggests that Fmr1 knockout mice may serve as a model for fragile X syndrome. The findings support the idea that FMRP is essential for the development of synaptic structures in the brain.