Isoform 2 of Peptidyl-prolyl cis-trans isomerase FKBP8

FKBP8 is a peptidyl-prolyl cis-trans isomerase (PPIase) encoded by the FKBP8 gene in humans (UniProt: Q14318-2). This isoform 2 variant is 413 amino acids in length and belongs to the FKBP immunophilin family, proteins that catalyze prolyl isomerization—a post-translational modification critical for protein folding and conformational dynamics.

FKBP8 is widely expressed across tissues and functions in protein quality control and cellular stress responses. The protein is localized to mitochondria and endoplasmic reticulum compartments, where it participates in proteostasis pathways. The UniProt record does not annotate specific disease associations in its curated sections.

In Alzheimer's disease, FKBP8 isoform 2 is downregulated in post-mortem human brain tissue from AD patients compared to age-matched controls (Chaparral AD proteomics). Quantitative proteomics analysis across subcellular fractions shows a mean log2 fold-change of −0.417, indicating modest but consistent reduction. This downregulation may reflect diminished proteostatic capacity in AD brains, as impaired protein folding and mitochondrial dysfunction are hallmarks of neurodegeneration in Alzheimer's pathology.