Stress-induced-phosphoprotein 1

Stress-induced-phosphoprotein 1 (STIP1) is a 543-amino-acid co-chaperone that facilitates protein folding and stability by mediating the functional interaction between HSP90AA1 and HSPA8/HSC70 (UniProt: P31948). It plays a central role in the molecular chaperone network, enabling client protein maturation and stress response.

STIP1 is expressed across human tissues and functions primarily in protein homeostasis pathways. UniProt records no primary disease associations for this protein, though its role in chaperone-mediated proteostasis implicates it in conditions marked by protein misfolding.

STIP1 was identified in Alzheimer's disease proteomics studies comparing post-mortem AD brain to age-matched controls using TMT-labeled tandem mass spectrometry across four subcellular fractions (Chaparral AD proteomics). The protein shows an ambiguous direction of change: the mean log2 fold-change across fractions is −0.1769, reflecting inconsistent regulation across the P2, P3, S2, and S3 fractions examined. This modest and variable change suggests STIP1 abundance is not substantially or uniformly altered in AD brain at the whole-tissue level.