PPIL3 (peptidylprolyl isomerase like 3) is a nuclear cyclophilin that catalyzes the cis-trans isomerization of proline imidic peptide bonds, accelerating protein folding 1. The gene is located on chromosome 2 and consists of eight exons spanning >18 kb, with ubiquitous expression in human tissues 1. PPIL3 functions as a splicing factor involved in pre-mRNA processing and is found in spliceosomal complexes 2. Mechanistically, PPIL3 interacts with viral proteins like SARS-CoV-2 NSP12, where it affects virus entry efficiency and polymerase activity while influencing alternative splicing of cellular genes 3. The protein also regulates cellular localization of cancer-selective proteins like Apoptin, sequestering it in the cytoplasm of tumor cells 4. Disease relevance includes associations with estrogen receptor-negative breast cancer susceptibility 5 and autoimmune hypothyroidism through brain-thyroid axis interactions 6. In bladder cancer, elevated PPIL3 expression promotes senescence markers and inhibits tumor cell proliferation 7. PPIL3 appears in gene regulatory networks associated with radiation-induced papillary thyroid carcinoma, suggesting involvement in carcinogenic processes including apoptosis and genomic instability 8. These findings establish PPIL3 as a multifunctional protein with roles in RNA processing, cancer biology, and therapeutic targeting.