Retinoic acid homeostasis and disease

Retinoids, particularly all-trans-retinoic acid (ATRA), play crucial roles in various physiological processes, including development, immune response, and reproduction, by regulating gene transcription through nuclear receptors. This review explores the biosynthetic pathways, homeostatic mechanisms, and the significance of retinoid-binding proteins in maintaining ATRA levels. It highlights the intricate balance required for ATRA homeostasis, emphasizing that both excess and deficiency can lead to severe developmental and health consequences. Furthermore, the associations are discussed between ATRA dysregulation and several diseases, including various genetic disorders, cancer, endometriosis, and heart failure, underscoring the role of retinoid-binding proteins like RBP1 in these conditions. The potential for gene-environment interactions in retinoid metabolism is also examined, suggesting that dietary factors may exacerbate genetic predispositions to ATRA-related pathologies. Methodological advancements in quantifying ATRA and its metabolites are reviewed, alongside the challenges inherent in studying retinoid dynamics. Future research directions are proposed to further elucidate the role of ATRA in health and disease, with the aim of identifying therapeutic targets for conditions linked to retinoid signaling dysregulation.