Lysine-specific demethylase RAD23A

RAD23A (lysine-specific demethylase RAD23A) is a multifunctional 39.6 kDa protein that catalyzes demethylation of histone H4 lysine 20 (H4K20me1/me2/me3) to modulate transcription of both coding genes and repetitive elements (UniProt: P54725). The protein also participates in nucleotide excision repair through interaction with XPC, ubiquitin-dependent proteasomal degradation, and viral replication processes. Its capacity to bind polyubiquitin chains and deliver substrates to the 26S proteasome positions it at the intersection of proteostasis and transcriptional regulation.

RAD23A is expressed broadly across tissues and associates with DNA repair and proteasomal function pathways. No non-AD disease associations are documented in UniProt. The protein has been implicated in HIV-1 replication in non-proliferating cells and primary macrophages through modulation of Vpr–proteasome interactions (UniProt: P54725).

In Alzheimer's disease, RAD23A shows increased abundance in post-mortem human AD brain tissue compared to age-matched controls, with a mean log2 fold-change of +0.46 (Chaparral AD proteomics). The upregulation was detected across a single subcellular fraction in a TMT-labeled proteomic study examining four fractions (P2, P3, S2, S3) from affected brain tissue, suggesting potential dysregulation of histone demethylation or proteostasis pathways in AD pathogenesis.