In the light of these premises and taking into account that: (1) HDAC9 is neurodetrimental in stroke 27; (2) HDACs, including HDAC9, can deacetylate transcription factors on lysine residues 28; (3) TfR1, Fpn1, and Ft expression are up-regulated by HIF-1; and (4) GPX4 transcription is up-regulated by Sp1; the aim of the present work was to determine the role played by HIF-1, Sp1, TfR1 and GPX4 in the signaling of ferroptotic neuronal death mediated by HDAC9 in in vitro and in vivo models of stroke. This evidence concerns the gene HDAC9 and stroke disorder.