PPIL2 (peptidylprolyl isomerase like 2) is a multifunctional protein that serves as both a U-box E3 ubiquitin ligase and a component of the minor spliceosome. As an E3 ligase, PPIL2 promotes protein degradation through Lys-48-linked polyubiquitination of key substrates including p53 1 and SNAI1 2. In the minor spliceosome, PPIL2 functions as a structural component that coordinates loop I of U5 snRNA and stabilizes U5 snRNP during splicing of rare U12-type introns 3. PPIL2 also regulates homologous recombination DNA repair by ubiquitinating CtIP at the K426 site, with this activity being modulated by PLK1 phosphorylation 4. Disease relevance includes roles in myeloproliferative neoplasms, where PPIL2 is upregulated as a STAT5 target and promotes cell proliferation by degrading p53 1, and in breast cancer metastasis, where it suppresses epithelial-mesenchymal transition through SNAI1 degradation 2. PPIL2 also positively regulates BACE1 mRNA levels, potentially impacting Alzheimer's disease pathogenesis 5. Clinically, PPIL2 represents a potential therapeutic target, as cyclosporin A treatment can inhibit its activity and reduce myeloproliferative phenotypes 1.