In Drosophila, the engrailed (en) gene plays an important role during development in segmentation, where it is required for the formation of posterior compartments.

The human engrailed homologs 1 and 2 encode homeodomain-containing proteins and have been implicated in the control of pattern formation during development of the central nervous system and the limbs.

[6] Engrailed (En) 1 is a homeobox gene that helps regulate development in the dorsal midbrain and anterior hindbrain (cerebellum and colliculi) of humans.

[7] A knockout mouse model with the En1 homeobox deleted was developed; mice died less than 24 hours after birth because appeared to be unable to feed.

[8] In 2021, a group of scientists and physicians around Andrea Superti-Furga in Lausanne and Stefan Mundlos in Berlin showed that biallelic loss-of-function variants at the EN1 locus result in a human phenotype that includes a severe impairment of limb development as well as cerebellar aplasia,[9] reproducing the phenotype first observed in the gene knock-out mice described above.