PPIE (peptidylprolyl isomerase E) is a dual-function protein that combines peptidyl-prolyl isomerase and RNA-binding activities 1. As a core spliceosomal component, PPIE participates in pre-mRNA splicing within the U2-type catalytic step 2 spliceosome 2. The protein catalyzes cis-trans isomerization of proline imidic peptide bonds in proteins 1 and preferentially binds single-stranded RNA molecules containing poly(A) and poly(U) stretches, particularly targeting the poly(A) region in mRNA 3'-UTRs 1. Functionally, PPIE inhibits KMT2A (a histone methyltransferase) activity through its proline isomerase function, suggesting regulatory roles in transcription 3. Disease relevance is indicated by PPIE's identification as a pathogenic target gene in gestational diabetes mellitus (GDM), where altered DNA methylation and differential expression correlate with metabolic dysfunction 4. The protein's involvement in both splicing and transcriptional regulation, combined with its association with metabolic disease pathways, suggests PPIE dysfunction may contribute to systemic metabolic disorders. Clinical significance remains to be fully established, though PPIE represents a potential diagnostic biomarker for GDM and type 2 diabetes prevention 4.