Adenylate kinase 2, mitochondrial

Adenylate kinase 2 (AK2) is a mitochondrial enzyme that catalyzes the reversible transfer of phosphate groups between ATP and AMP, playing a central role in cellular energy homeostasis and adenine nucleotide metabolism (UniProt: P54819). The protein is particularly important for regulating phosphate utilization and AMP biosynthesis pathways, and has been implicated in hematopoiesis. Mutations in AK2 cause reticular dysgenesis, a severe autosomal recessive immunodeficiency characterized by absent granulocytes and lymphocyte deficiency.

AK2 shows increased expression in post-mortem Alzheimer's disease brain tissue compared to age-matched controls, with a mean log2 fold-change of +0.41 detected via TMT-labeled proteomics across subcellular fractions (Chaparral AD proteomics). This upregulation suggests a potential compensatory metabolic response or altered energy metabolism in the AD brain. The functional relevance of elevated AK2 in AD pathology warrants further investigation, particularly given the protein's critical role in mitochondrial bioenergetics.