M6A Demethylase ALKBH5 in Human Diseases: From Structure to Mechanisms

N6-methyladenosine (m6A) is the most abundant, dynamically reversible, and evolutionarily conserved internal chemical modification in eukaryotic RNA. It is emerging as critical for regulating gene expression at the post-transcriptional level by affecting RNA metabolism through, for example, pre-mRNA processing, mRNA decay, and translation. ALKBH5 has recently been identified as an endogenous m6A demethylase implicated in a multitude of biological processes. This review provides an overview of the structural and functional characteristics of ALKBH5 and the involvement of ALKBH5 in diverse human diseases, including metabolic, immune, reproductive, and nervous system disorders, as well as the development of inhibitors. In summation, this review highlights the current understanding of the structure, functions, and detailed mechanisms of ALKBH5 in various physiological and pathological processes and provides valuable insights for clinical applications and foundational research within related fields.