The longstanding puzzle of why females develop autism at roughly one-quarter the rate of males may finally have a biological explanation that could reshape understanding of sex-based disease resistance. This protective advantage extends beyond autism to numerous male-biased developmental disorders, suggesting a fundamental mechanism governing genetic vulnerability across sexes. Researchers propose that females gain resilience through an unexpected source: their supposedly "inactive" X chromosome continues producing proteins from specific genes, creating a buffer against harmful genetic mutations. This challenges the conventional view that one X chromosome becomes completely silenced during female development. The dual expression from both active and inactive X chromosomes appears to provide females with higher levels of certain protective proteins. These elevated protein concentrations help neutralize the effects of damaging mutations in autosomal genes—the 22 pairs of chromosomes shared by both sexes. The mechanism appears particularly effective against mutations affecting pathways that the inactive X chromosome also regulates, creating redundant protection systems. This framework explains why females require a substantially higher burden of autism-associated genetic variants before manifesting symptoms, while males with identical mutations may develop the condition. The protective effect appears consistent across multiple male-biased conditions, including intellectual disability and attention deficit disorders. However, this research represents theoretical modeling rather than experimental validation. The hypothesis requires testing through direct measurement of protein expression from inactive X chromosomes in affected individuals. If confirmed, this could fundamentally alter therapeutic approaches, suggesting treatments might need sex-specific dosing or that enhancing X-linked gene expression could provide protective benefits across multiple developmental disorders.