Following crystallographic studies revealing that the Traboulsi syndrome–associated variations in the AspH active site can alter the nature of 2OG binding, we demonstrate proof-of-principle evidence showing the potential of synthetic and naturally occurring 2-oxoacids, including amino acid transamination products abundant in cells, to compensate for the reduced activity of Traboulsi syndrome–associated variants, highlighting the therapeutic possibility of rescuing the activity of pathogenic AspH variants. Here, ASPH is linked to facial dysmorphism-lens dislocation-anterior segment abnormalities-spontaneous filtering blebs syndrome.