The paper identifies a new retinoid response pathway mediated by 9-cis retinoic acid (9cRA) and the nuclear receptor LXRα. LXRα, a member of the nuclear receptor superfamily, is specifically expressed in visceral organs and activates transcription through a distinct response element called the LXRE. The interaction between LXRα and endogenous RXR allows RXR to function as an active, ligand-binding partner, shifting its role from a silent, DNA-binding partner to an active, ligand-binding subunit in mediating retinoid responses. This interaction is unique to LXRα and RXR, as neither RXR homodimers nor RXR/RAR heterodimers can substitute for LXRα in this process. The findings establish a new pathway for RXR to function as a potent 9cRA receptor with a distinct target gene specificity.The paper identifies a new retinoid response pathway mediated by 9-cis retinoic acid (9cRA) and the nuclear receptor LXRα. LXRα, a member of the nuclear receptor superfamily, is specifically expressed in visceral organs and activates transcription through a distinct response element called the LXRE. The interaction between LXRα and endogenous RXR allows RXR to function as an active, ligand-binding partner, shifting its role from a silent, DNA-binding partner to an active, ligand-binding subunit in mediating retinoid responses. This interaction is unique to LXRα and RXR, as neither RXR homodimers nor RXR/RAR heterodimers can substitute for LXRα in this process. The findings establish a new pathway for RXR to function as a potent 9cRA receptor with a distinct target gene specificity.