A study published in the Journal of Clinical Investigation examined the GABRA3 gene, linked to epilepsy and located on the X chromosome. Researchers analyzed a group of 43 individuals with 19 variants of the GABRA3 gene, uncovering both gain- and loss-of-function effects tied to different clinical outcomes. Gain-of-function variants were associated with severe, treatment-resistant epilepsy and significant intellectual disabilities, primarily affecting males, who often experienced severe mobility issues and visual impairments. In contrast, loss-of-function variants led to milder symptoms, with epilepsy being rare. Males with these variants exhibited behavioral challenges and language delays, while female carriers typically showed no symptoms. A mouse model of the gain-of-function variant replicated these sex-specific effects, displaying increased susceptibility to seizures and early death. This research clarifies the role of GABRA3 in epilepsy and suggests that the functional impact of a variant is more significant than its mere presence in determining whether a condition appears dominantly or recessively. These findings have vital implications for genetic counseling, precision medicine, and understanding X-linked neurodevelopmental disorders.