In this discovery study, we have utilized a 2D-DIGE coupled with tandem MS to identify 6 candidate CSF protein markers for early-onset Restless Legs Syndrome (RLS/WED); four proteins (Cystatin C, Lipocalin-type Prostaglandin D2 Synthase, Vitamin D binding Protein, and β-Hemoglobin) were increased and 2 proteins (Apolipoprotein A1 and α-1-acid Glycoprotein) were decreased in RLS/WED patients compared to controls. Here, CST3 is linked to restless legs syndrome.