We propose the dimorphic overexpression of X-linked proteins, such as CXorf21 and TLR7, which the present work shows interact functionally in innate immune responses, contribute to the pathogenesis of female-biased autoimmune disorders such as SLE and pSS, and may explain, in part, the propensity for women to have these diseases. Here, PSMB5 is linked to peeling skin syndrome.