Alpha-actinin-2

Alpha-actinin-2 (ACTN2) is an F-actin cross-linking protein that anchors actin filaments to intracellular structures and functions as a bundling protein (UniProt: P35609). The protein is widely expressed and plays a structural role in cytoskeletal organization across multiple cell types.

UniProt documentation associates ACTN2 variants with several muscular and cardiac disorders, including familial hypertrophic cardiomyopathy (CMH23), dilated cardiomyopathy (CMD1AA), congenital myopathy 8 (CMYO8), and adult-onset distal myopathy 6 (MPD6), reflecting its critical role in sarcomeric and cytoskeletal integrity (UniProt: P35609).

Alpha-actinin-2 is down-regulated in Alzheimer's disease brain tissue. Analysis of post-mortem AD brain versus age-matched controls using TMT-labeled proteomics across subcellular fractions demonstrated reduced abundance with a mean log2 fold-change of −0.98 (Chaparral AD proteomics). The functional significance of this down-regulation in AD pathology remains to be determined.