Retinoic Acid Receptor gamma (RAR gamma) is a member of the Retinoic Acid Receptor family. Retinoids, vitamin A and its natural and synthetic analogues, are a very important group of hormones that regulate a wide variety of biological functions including embryogenesis, cell growth, and cell differentiation. Retinoids have a wide variety of clinical benefit, they have uses in dermatology, oncology, diabetes, and diseases associated with HPV. Non-selective retinoids are usually associated with toxicity problems that limit their therapeutic usefulness. RAR gamma is the predominant RAR subtype present in the skin and it constitutes more than 90% of the total skin or keratinocyte RAR repertoire. Skin irritation is a classical toxicity associated with RAR pan-agonists, like RA or TTNPB, and is believed to be a manifestation of RAR gamma activation. Furthermore, it has been shown that tumorspecific apoptosis can be driven by RAR gamma selective agonists, for pancreatic cancer cells. RAR beta and gamma are significantly different from RAR alpha in the way they bind to co-repressors. RAR beta and gamma have a fully functional SMRT docking site but the access of SMRT to this docking site is blocked by helix 12, which in RAR beta and gamma assumes a sequestered position in the absence of hormone. This ultimately leads to high basal levels of transcription even in the absence of ligand. This transcriptional activity can, however, be increased with the addition of the ligand alltrans retinoic acid (ATRA).