Profilin-1

Profilin-1 (PFN1) is a 140-amino acid actin-binding protein that regulates cytoskeletal dynamics through concentration-dependent mechanisms (UniProt: P07737). At high concentrations it inhibits actin polymerization while promoting it at low levels; the protein also binds phosphatidylinositol 4,5-bisphosphate to suppress inositol 1,4,5-trisphosphate and diacylglycerol formation, and it inhibits androgen receptor and huntingtin aggregation.

Profilin-1 is widely expressed and participates in fundamental cellular processes governing cytoskeletal organization and signal transduction. Beyond its canonical actin-regulatory role, the protein has been associated with amyotrophic lateral sclerosis 18 (ALS18; MIM 614808), a neurodegenerative condition characterized by motor neuron loss and pathologic protein aggregates.

In Alzheimer's disease, profilin-1 shows increased abundance in post-mortem AD brain tissue compared to age-matched controls (Chaparral AD proteomics). The protein was significantly upregulated with a mean log2 fold-change of 0.97 across the analyzed subcellular fractions in TMT-labeled proteomics experiments, suggesting potential involvement in AD-associated pathology, though the functional consequence of this elevation remains to be elucidated.