CWC27 is a spliceosome-associated cyclophilin that functions as a core component of the pre-mRNA splicing machinery 1. Unlike typical cyclophilins, CWC27 is a probable inactive peptidyl-prolyl cis-trans isomerase lacking enzymatic PPIase activity 2. Instead, it acts as a structural protein within the spliceosome, participating in catalytic splicing steps and potentially in U12-type minor spliceosome function. CWC27 forms a functional heterodimer with CWC22 that links the exon junction complex to spliceosomes, serving as an intermediate landing platform during spliceosome assembly 3. Biallelic CWC27 mutations cause CWC27-related spliceosomopathy, a rare autosomal recessive disorder 4. Disease pathophysiology involves disrupted pre-mRNA splicing, with particular sensitivity in neural crest cell-derived tissues, likely through p53-mediated cell death pathways 5. Clinical manifestations include early-onset retinitis pigmentosa with chorioretinal atrophy 4, skeletal anomalies, short stature, and distinctive ectodermal features (sparse hair, nail dysplasia, dental anomalies) 6. Additional systemic involvement may include craniofacial malformations, neurological defects, and immune abnormalities 7. Gene augmentation therapy via AAV8-mediated CWC27 delivery successfully rescued retinal degeneration in Cwc27 mutant mice 8, suggesting therapeutic potential for this severe spliceosomopathy.