Although HDAC2 isoform-specific deacetylase inhibition did not replicate the profound IRI protection seen in HDAC2 deletion within the kidney, pharmacologic approaches to either inhibit HDAC2 occupancy in the CoREST complex, stabilize the CoREST complex itself, or alter Edn1 expression, as well as HDAC2 knockdown by antisense oligonucleotides, offer promising avenues to interrupt AKI development. Here, HDAC2 is linked to acute kidney injury.