We therefore decided to interrogate the biochemical basis for the cooperation of Sox and Pax TFs to (i) uncover the sequence determinants for the cooperative interactions, (ii) understand the biochemical and structural basis for the cooperative formation of ternary complexes, (iii) ask if there is a Sox–Pax partner code that determines target gene selection, (iv) assess whether mutations within Sox2 and Pax6 causative of congenital human eye disorders alter Sox2–Pax6 cooperativity and (v) identify novel Sox/Pax target site in the human genome that supports cooperative interactions. Here, SOX2 is linked to eye disorder.