The　nuclear　receptor　RXRα　(retinoid　X　receptor-α)　is　a　transcription　factor　that　regulates　the　expression　of　multiple　genes.　Its　non-genomic　function　is　largely　related　to　its　structure,　polymeric　forms　and　modification.　Previous　research　revealed　that　some　non-genomic　activity　of　RXRα　occurs　via　formation　of　heterodimers　with　Nur77.　RXRα–Nur77　heterodimers　translocate　from　the　nucleus　to　the　mitochondria　in　response　to　certain　apoptotic　stimuli　and　this　activity　correlates　with　cell　apoptosis.　More　recent　studies　revealed　a　significant　role　for　truncated　RXRα　(tRXRα),　which　interacts　with　the　p85α　subunit　of　the　PI3K/AKT　signaling　pathway,　leading　to　enhanced　activation　of　AKT　and　promoting　cell　growth　in　vitro　and　in　animals.　We　recently　reported　on　a　series　of　NSAID　sulindac　analogs　that　can　bind　to　tRXRα　through　a　unique　binding　mechanism.　We　also　identified　one　analog,　K-80003,　which　can　inhibit　cancer　cell　growth　by　inducing　tRXRα　to　form　a　tetramer,　thus　disrupting　p85α–tRXRα　interaction.　This　review　analyzes　the　non-genomic　effects　of　RXRα　in　normal　and　tumor　cells,　and　discusses　the　functional　differences　based　on　RXRα　protein　structure　(structure　source:　the　RCSB　Protein　Data　Bank).　©　2018,　The　Author(s).