NKX2.1 may play a role in Hirschsprung disease, a disorder of the developing enteric nervous system, through its interaction with SOX10 and PAX3. Sex-determining factor SRY is reported to displace SOX10’s interaction with NKX2.1 and PAX3, thereby promoting a Hirschsprung disease phenotype (Li et al., 2015). Here, NKX2-1 is linked to Hirschsprung disease.