Inverted formin-2

Inverted formin-2 (INF2) is a 1249-amino acid protein that severs actin filaments while accelerating their polymerization and depolymerization (UniProt: Q27J81). It plays a critical regulatory role in cytoskeletal dynamics through direct modulation of actin filament turnover.

INF2 is primarily associated with renal and peripheral nervous system pathologies. Mutations in INF2 cause focal segmental glomerulosclerosis 5 (FSGS5), characterized by progressive renal dysfunction and proteinuria, and Charcot-Marie-Tooth disease, dominant intermediate E (CMTDIE), which combines peripheral neuropathy with glomerulonephritis and renal decline (UniProt: Q27J81).

In Alzheimer's disease, INF2 is significantly downregulated in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of −0.417 (Chaparral AD proteomics). This downregulation was detected across the analyzed subcellular fractions in TMT-labeled quantitative proteomics, suggesting reduced cytoskeletal remodeling capacity may contribute to AD pathophysiology. The functional significance of diminished INF2 in AD neurodegeneration warrants further investigation.