PPIL4 (peptidylprolyl isomerase like 4) is a nuclear RNA-binding protein located on chromosome 6-q25 that functions as a peptidyl-prolyl cis-trans isomerase involved in protein folding 1. Beyond its canonical PPIase activity, PPIL4 contains an RNA recognition motif and plays critical roles in pre-mRNA splicing. Structurally, PPIL4 functions as a component of the spliceosomal catalytic activation pathway, where it assembles with PRP2 helicase to regulate translocation termination during the transition from Bact to B* spliceosomes 2. At the molecular level, PPIL4 is ubiquitinated by USP7, a deubiquitinase; USP7-mediated PPIL4 deubiquitination regulates splicing of synaptic genes and dendritic spinogenesis 3. PPIL4 is also implicated in vascular development, where it potentiates Wnt signaling by binding JMJD6 to regulate brain angiogenesis and cerebrovascular integrity 4. Clinically, rare deleterious mutations in PPIL4 are enriched in familial and sporadic intracranial aneurysm cases, and loss of PPIL4 function causes intracerebral hemorrhage and impaired Wnt signaling 4. Additionally, PPIL4 represents a novel drug target for CRBN-mediated protein degradation 5. These findings position PPIL4 as a multifunctional protein essential for splicing regulation, neuronal connectivity, and cerebrovascular homeostasis.