Rxra, short for Retinoic acid X receptor alpha, is a member of the nuclear receptor superfamily. It is involved in multiple biological processes such as lipid, glucose, energy, and hormone metabolism [3]. Rxra often forms heterodimers with other nuclear receptors like peroxisome proliferator-activated receptors (PPARs) to regulate transcription, and is associated with pathways such as RA/RXRA/ANGPT1 [2]. It has significance in processes from adipogenesis to vascular normalization and plays a role in diseases including leukemia and bladder cancer.

In leukemia, deletion of Rxra and Rxrb in mice augments leukemic growth. An unexpected discovery was the identification of the constitutively active variant RXRA DT448/9PP in murine KMT2A-MLLT3 leukemia cells, which can induce maturation and loss of the proliferative phenotype of leukemia cells [1]. In lung adenocarcinoma, CCL28-recruited pericytes promote vascular normalization after anti-angiogenesis therapy through the RA/RXRA/ANGPT1 pathway [2]. In ducks, the RXRA gene promotes adipogenesis and its SNPs are related to feed efficiency traits [3]. In atherosclerotic mice, inhibition of the RXRA-PPARα-FABP4 signaling pathway by an SGLT2 inhibitor alleviates vascular cellular aging [4]. In a sheep model of maternal undernutrition, the PPARA/RXRA signalling pathway regulates hepatic lipid metabolism [5]. In bladder cancer, RXRA hot-spot mutations can activate PPARs to drive urothelial proliferation [6].

In conclusion, Rxra is crucial in various biological functions and disease conditions. Through studies using mouse models and other experimental systems, its roles in lipid metabolism, cell maturation, and disease-associated processes have been revealed. These findings contribute to understanding the underlying mechanisms of diseases such as leukemia, lung cancer, atherosclerosis, and bladder cancer, providing potential targets for therapeutic interventions.