Retinoid X receptors (RXRs) are nuclear receptors that function as transcriptional activators. In response to retinoids, they bind to specific cis-acting RXR responsive promoter elements of the cellular retinol-binding protein II promoter. The TGIF1 gene encodes an atypical homeobox protein that competitively inhibits this binding, thereby inhibiting the 9-cis-retinoic acid-dependent RXR alpha transcription activation of the retinoic acid responsive element. TGIF1 also acts as a transcriptional co-repressor of SMAD2. By carrying out its functions, the protein plays a role in the cellular response to growth factor stimulus and is thus an important embryonic development protein.
Mutations in the TGIF1 gene have been associated with Holoprosencephaly 4 (HPE4), an autosomal dominant neurological condition.