PFDN2 (prefoldin subunit 2) is a molecular chaperone that binds to nascent polypeptide chains and facilitates their transfer to cytosolic chaperonin complexes, promoting proper protein folding 1. Beyond its canonical chaperone role, PFDN2 regulates γ-synuclein (SNCG) expression in retinal ganglion cells, with shared mitochondrial functions between these proteins 2. PFDN2 demonstrates significant clinical relevance across multiple disease contexts. In colorectal cancer, PFDN2 functions as a hub gene in a ribosome biogenesis-related prognostic signature, with elevated expression correlating with poor outcomes; PFDN2 knockdown promotes cancer cell proliferation, migration, and invasion 1. Similarly, high PFDN2 expression predicts poor overall survival in gastric cancer across multiple patient subsets 3. Conversely, plasma PFDN2 acts as a protective factor against head and neck squamous cell carcinoma by suppressing CD64 on monocytes and restricting inflammatory microenvironments 4. In type 2 diabetes, autoantibodies against PFDN2 are associated with increased disease risk, particularly in early-onset cases 5. Additionally, PFDN2 is implicated in genetic associations with Alzheimer's disease through pathway analysis 6, and participates in gene regulatory networks affecting myelodysplastic syndrome treatment response 7. These findings establish PFDN2 as a multifunctional protein with context-dependent roles in protein homeostasis and disease pathogenesis.