The　nuclear　receptor　RXR　alpha　(retinoid　X　receptor-alpha)　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　RXR　alpha　occurs　via　formation　of　heterodimers　with　Nur77.　RXR　alpha-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　RXR　alpha　(tRXR　alpha),　which　interacts　with　the　p85　alpha　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　tRXR　alpha　through　a　unique　binding　mechanism.　We　also　identified　one　analog,　K-80003,　which　can　inhibit　cancer　cell　growth　by　inducing　tRXR　alpha　to　form　a　tetramer,　thus　disrupting　p85　alpha-tRXR　alpha　interaction.　This　review　analyzes　the　non-genomic　effects　of　RXR　alpha　in　normal　and　tumor　cells,　and　discusses　the　functional　differences　based　on　RXR　alpha　protein　structure　(structure　source:　the　RCSB　Protein　Data　Bank).