Protein flightless-1 homolog

Protein flightless-1 homolog (FLII) is an actin-binding regulator that controls cytoskeletal dynamics and myofibril organization. It inhibits Rac1-dependent signaling to modulate cell migration and cytokinesis, and functions as a coactivator in hormone-activated nuclear receptor signaling pathways (UniProt: Q13045). The protein is primarily studied in cardiac and cytoskeletal contexts, with mutations associated with autosomal recessive dilated cardiomyopathy (CMD2J; MIM 620635).

In Alzheimer's Disease, FLII shows a consistent downregulation in post-mortem AD brain tissue compared to age-matched controls (Chaparral AD proteomics). Quantitative proteomics analysis using TMT labeling across four subcellular fractions yielded a mean log2 fold-change of −0.0831, indicating modest but reproducible decreased abundance. This suggests potential involvement of actin cytoskeletal dysregulation in AD pathology, though the functional consequences remain to be clarified.